Prochlorperazine

Before staring prochlorperazine, tell your doctor about any prescription, non-prescription, over-the-counter (OTC), illegal and recreational drugs, herbal remedies, nutritional and dietary supplements, and all other drugs and treatments you're taking.

Prochlorperazine and Drug Interactions

If you are taking any of the following medications while taking prochlorperazine, your doctor will watch closely to guard against interactions:

• Thiazide diuretics, such as hydrochlorothiazide (Microzide) or chlorothiazide (Diuril). These can lower blood pressure too much when taken with prochlorperazine.
• Oral anticoagulants such as warfarin (Coumadin) can work less effectively when taken with prochlorperazine.
• Anticonvulsant medications (anti-epileptic drugs) may need to be dose-adjusted.

Prochlorperazine and Alcohol

Prochlorperazine may intensify or lengthen the effects of alcohol. Ask your doctor about using alcohol while taking prochlorperazine.

Increased Mortality In Elderly Patients With Dementia-Related Psychosis

Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Compazine® Prochlorperazine Suppositories USP is not approved for the treatment of patients with dementia-related psychosis (see BOXED WARNING).

The extrapyramidal symptoms which can occur secondary to prochlorperazine may be confused with the central nervous system signs of an undiagnosed primary disease responsible for the vomiting, e.g., Reye’s Syndrome or other encephalopathy. The us e of prochlorperazine and other potential hepatotoxins should be avoided in children and adolescents whose signs and symptoms suggest Reye’s Syndrome.

Tardive Dyskinesia

Tardive dyskinesia, a syndrome consisting of potentially irreversible, involuntary, dyskinetic movements, may develop in patients treated with neuroleptic (antipsychotic) drugs. Although the prevalence of the syndrome appears to be highest among the elderly, 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. Whether neuroleptic drug products differ in their potential to cause tardive dyskinesia is unknown.

Both the risk of developing the syndrome and the likelihood that it will become irreversible are believed to increase as the duration of treatment and the total cumulative dose of neuroleptic drugs administered to the patient increase. However, the syndrome can develop, although much less commonly, after relatively brief treatment periods at low doses.

There is no known treatment for established cases of tardive dyskinesia, although the syndrome may remit, partially or completely, if neuroleptic treatment is withdrawn. Neuroleptic treatment itself, however, may suppress (or partially suppress) the signs and symptoms of the syndrome and thereby may possibly mask the underlying disease process.

The effect that symptomatic suppression has upon the long-term course of the syndrome is unknown. Given these considerations, neuroleptics should be prescribed in a manner that is most likely to minimize the occurrence of tardive dyskinesia. Chronic neuroleptic treatment should generally be reserved for patients who suffer from a chronic illness that, 1) is known to respond to neuroleptic drugs, and 2) for whom alternative, equally effective, but potentially less harmful treatments are not available or appropriate. In patients who do require chronic treatment, the smallest dose and the shortest duration of treatment producing a satisfactory clinical response should be sought. The need for continued treatment should be reassessed periodically.

If signs and symptoms of tardive dyskinesia appear in a patient on neuroleptics, drug discontinuation should be considered. However, some patients may require treatment despite the presence of the syndrome.

For further information about the description of tardive dyskinesia and its clinical detection, please refer to the sections on PRECAUTIONS and ADVERSE REACTIONS.

Neuroleptic Malignant Syndrome (NMS)

A potentially fatal symptom complex some- times referred to as Neuroleptic Malignant Syndrome (NMS) has been reported in association with antipsychotic drugs. Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis and cardiac dysrhythmias).

The diagnostic evaluation of patients with this syndrome is complicated. In arriving at a diagnosis, it is important to identify cases where the clinical presentation includes both serious medical illness (e.g., pneumonia, systemic infection, etc.) and untreated or inad- equately treated extrapyramidal signs and symptoms (EPS). Other important considerations in the differential diagnosis include central anticholinergic toxicity, heat stroke, drug fever and primary central nervous system (CNS) pathology. The management of NMS should include 1) immediate discontinuation of antipsychotic drugs and other drugs not essential to concurrent therapy, 2) intensive symptomatic treatment and medical monitoring, and 3) treatment of any concomitant serious medical problems for which specific treatments are available. There is no general agreement about specific pharmacological treatment regimens for uncomplicated NMS.

If a patient requires antipsychotic drug treatment after recovery from NMS, the potential reintroduction of drug therapy should be carefully considered. The patient should be carefully monitored, since recurrences of NMS have been reported.

General

Patients with bone marrow depression or who have previously demonstrated a hypersensitivity reaction (e.g., blood dyscrasias, jaundice) with a phenothiazine should not receive any phenothiazine, including prochlorperazine, unless in the judgment of the physician the potential benefits of treatment outweigh the possible hazards. Prochlorperazine may impair mental and/or physical abilities, especially during the first few days of therapy. Therefore, caution patients about activities requiring alertness (e.g., operating vehicles or machinery).

Phenothiazines may intensify or prolong the action of central nervous system depressants (e.g., alcohol, anesthetics, narcotics).

Usage In Pregnancy

Safety for the use of prochlorperazine during pregnancy has not been established. Therefore, prochlorperazine is not recommended for use in pregnant patients except in cases of severe nausea and vomiting that are so serious and intractable that, in the judgment of the physician, drug intervention is required and potential benefits outweigh possible hazards.

There have been reported instances of prolonged jaundice, extrapyramidal signs, hyperreflexia or hyporeflexia in newborn infants whose mothers received phenothiazines.

Nursing Mothers

There is evidence that phenothiazines are excreted in the breast milk of nursing mothers.

Prochlorperazine may be found in some form under the following brand names:

• Compazine

• Compro

• Procot

Prochlorperazine is part of the drug class:

• Phenothiazines with piperazine structure

You should not use prochlorperazine if you are allergic to it, or if you have recently used alcohol, sedatives, tranquilizers, or narcotic medications.

Prochlorperazine is not approved for use in psychotic conditions related to dementia. Prochlorperazine may increase the risk of death in older adults with dementia-related conditions.

Prochlorperazine is not approved for use by anyone younger than 2 years old or weighing less than 20 pounds. Talk with your doctor before giving prochlorperazine to a child or teenager with a fever, flu symptoms, vomiting, or diarrhea.

Do not give this medicine to a child before or after a surgery.

Long-term use of prochlorperazine can cause a serious movement disorder that may not be reversible. The longer you take prochlorperazine, the more likely you are to develop this movement disorder. The risk of this side effect is higher in women and older adults.

To make sure prochlorperazine is safe for you, tell your doctor if you have ever had:

• urination problems;

• a blockage in your intestines;

• glaucoma;

• heart disease;

• low blood pressure;

• breast cancer;

• liver disease;

• adrenal gland tumor (pheochromocytoma);

• seizures, or a history of brain tumor;

• Parkinson's disease; or

• a serious side effect while using prochlorperazine or another phenothiazine.

Tell your doctor if you will be exposed to extreme heat or cold, or to insecticide poisons while you are taking prochlorperazine.

It is not known whether this medicine will harm an unborn baby. Tell your doctor if you are pregnant.

Taking antipsychotic medicine in the last 3 months of pregnancy may cause problems in the newborn, such as withdrawal symptoms, breathing problems, feeding problems, fussiness, tremors, and limp or stiff muscles. However, you may have withdrawal symptoms or other problems if you stop taking your medicine during pregnancy. If you become pregnant, do not stop taking prochlorperazine without your doctor's advice.

Prochlorperazine can pass into breast milk and may harm a nursing baby. Tell your doctor if you are breast-feeding a baby.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Overdose can cause severe drowsiness, irregular heartbeats, agitation, seizure, or fainting.

General

• Adjust dosage carefully according to individual requirements and response; use the lowest possible effective dosage.100 d f g

• Periodically evaluate patients receiving long-term therapy to determine whether maintenance dosage can be decreased or drug therapy discontinued.100 d f g (See Tardive Dyskinesia under Cautions.)

Psychotic Disorders

• Symptomatic relief of psychotic disorders may be seen in many patients during the first 2 days of therapy; however, optimum antipsychotic effect usually requires prolonged administration of the drug.d

• For prompt control of severe psychotic symptoms, administer IM; after symptoms are controlled, oral therapy should replace parenteral therapy at the same dosage level or higher.d

Administration

Prochlorperazine edisylate is administered by deep IM injection, direct IV injection, or IV infusion.a d f

Prochlorperazine maleate is administered orally as conventional tablets.100 a d

Prochlorperazine is administered rectally.a g

Sub-Q administration of prochlorperazine edisylate is not recommended because of local irritation.d f

IV Administration

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

May be administered undiluted or diluted in isotonic solution.f

To minimize hypotension following IV administration, patient should remain in supine position under observation for ≥30 minutes.100 f (See Hypotension under Cautions.)

Administer by IV infusion or by direct IV injection at a rate not exceeding 5 mg/minute.a f

Do not administer as a rapid (“bolus”) injection.a f

IM Administration

Administer by deep IM injection into the upper outer quadrant of the gluteus maximus.a b d f

If possible, avoid IM administration in geriatric patients who are thin or debilitated with reduced muscle mass (injections may be painful and absorption may be erratic or unpredictable).b

Dosage

Available as prochlorperazine, prochlorperazine edisylate, or prochlorperazine maleate; dosage expressed in terms of prochlorperazine.a d

Pediatric Patients

Children should receive the lowest possible effective dosage, and parents should be instructed not to exceed the prescribed dosage.100 d f

Use not recommended in children <2 years of age or those weighing <9 kg.100 d

Children 2–12 years of age: Initially, 2.5 mg 2 or 3 times daily; total dosage should not exceed 10 mg on first day.100 d May increase dosage according to patient’s therapeutic response and tolerance, but usually should not exceed 20 and 25 mg daily for children 2–5 and 6–12 years of age, respectively.100 d

Dosage for children <2 years of age or those weighing <9 kg not established.100 d

Children <12 years of age: 0.13 mg/kg.d f Generally, most pediatric patients respond after 1 dose, and oral therapy should replace parenteral therapy at the same dosage level or higher.d f

Alternatively, in children ≥2 years of age and weighing >9 kg: 0.4 mg/kg or 10 mg/m2 daily given in 3 or 4 divided doses.a

Generally, it is not necessary to continue therapy for >24 hours.100 a

Children ≥2 years of age and weighing >9 kg: 0.13 mg/kg.a f Generally, a single dose is sufficient to control nausea and vomiting in most patients.a f

Adults

5 or 10 mg 3 or 4 times daily in office patients and outpatients with relatively mild symptomatology.100 d

Initially, 10 mg 3 or 4 times daily for hospitalized or well-supervised patients with moderate to severe symptomatology.100 d Gradually increase dosage every 2 or 3 days until symptoms are controlled or adverse effects become troublesome.100 d Although some patients exhibit optimum response with 50–75 mg daily, dosages of 100–150 mg daily usually required in more severely disturbed patients.100 d

10–20 mg for prompt control in patients with severe symptomatology; may be necessary to repeat the initial dose every 1–4 hours to control symptoms in some patients.d f Generally, not more than 3 or 4 doses are required.d f

10–20 mg every 4–6 hours, if prolonged parenteral therapy is required.d f

After the patient’s symptoms are controlled, oral therapy should replace parenteral therapy at the same dosage level or higher.d f

5 mg 3 or 4 times daily for ≤12 weeks.100 d

Usually, 5 or 10 mg 3 or 4 times daily.100 a

Dosages >40 mg daily should be used only in resistant cases.100 a

25 mg twice daily.g

2.5–10 mg.a f

For control of severe nausea and vomiting during surgery: 5–10 mg given 15–30 minutes before induction of anesthesia.a f If necessary, repeat initial dose once before surgery.a f

To control acute symptoms during or after surgery, usually 5–10 mg, repeated once, if necessary; single IV doses of the drug should not exceed 10 mg.a f

Initially, 5–10 mg; if necessary, initial dose may be repeated every 3 or 4 hours, but total dosage should not exceed 40 mg daily.a f

For control of severe nausea and vomiting during surgery: 5–10 mg given 1–2 hours before induction of anesthesia.a f If necessary, dose may be repeated once, 30 minutes after the initial dose.a f

To control acute symptoms during or after surgery: 5–10 mg, repeated once in 30 minutes, if necessary.a f

Prescribing Limits

Pediatric Patients

Maximum 10 mg daily for the first day.100 d

Subsequently, maximum 20 and 25 mg daily for children 2–5 and 6–12 years of age, respectively.100 d

Adults

Maximum 20 mg daily; do not administer for >12 weeks.100

Dosages >40 mg daily should be used only in resistant cases.100 a

Maximum 10 mg as a single dose.a f Maximum 40 mg daily (total daily dosage).a f

Maximum 40 mg daily (total daily dosage).a f

Special Populations

Geriatric Patients

Generally, select dosage at lower end of recommended range; increase dosage gradually and monitor closely.100 d f g (See Geriatric Use under Cautions.)

Debilitated or Emaciated Patients

Increase dosage gradually.100 d f g

Leukopenia, Neutropenia and Agranulocytosis

In clinical trial and postmarketing experience, events of leukopenia/neutropenia and agranulocytosis have been reported temporally related to antipsychotic agents.

Possible risk factors for leukopenia/neutropenia include preexisting low white blood cell count (WBC) and history of drug induced leukopenia/neutropenia. Patients with a preexisting low WBC or a history of drug induced leukopenia/neutropenia should have their complete blood count (CBC) monitored frequently during the first few months of therapy and should discontinue Prochlorperazine Edisylate Injection USP at the first sign of a decline in WBC in the absence of other causative factors.

Patients with neutropenia should be carefully monitored for fever or other symptoms or signs of infection and treated promptly if such symptoms or signs occur. Patients with severe neutropenia (absolute neutrophil count <1000/mm3) should discontinue Prochlorperazine Edisylate Injection USP and have their WBC followed until recovery.

Prochlorperazine’s antiemetic action may mask signs and symptoms of overdosage of other drugs and may obscure the diagnosis and treatment of other conditions such as intestinal obstruction, brain tumor and Reye’s syndrome (see WARNINGS).

When Prochlorperazine is used with cancer chemotherapeutic drugs, vomiting as a sign of toxicity of these agents may be obscured by the antiemetic effect of Prochlorperazine.

Because hypotension may occur, large doses and parenteral administration should be used cautiously in patients with impaired cardiovascular systems. To minimize the occurrence of hypotension after injection, keep patient lying down and observe for at least 1/2 hour. If hypotension occurs after parenteral dosing, place patient in head-low position with legs raised. If a vasoconstrictor is required, norepinephrine and phenylephrine are suitable. Other pressor agents, including epinephrine, should not be used because they may cause a paradoxical further lowering of blood pressure.

Aspiration of vomitus has occurred in a few postsurgical patients who have received Prochlorperazine as an antiemetic. Although no causal relationship has been established, this possibility should be borne in mind during surgical aftercare.

Deep sleep, from which patients can be aroused, and coma have been reported, usually with overdosage.

Antipsychotic drugs elevate prolactin levels; the elevation persists during chronic administration. Tissue culture experiments indicate that approximately one-third of human breast cancers are prolactin-dependent in vitro, a factor of potential importance if the prescription of these drugs is contemplated in a patient with a previously detected breast cancer. Although disturbances such as galactorrhea, amenorrhea, gynecomastia, and impotence have been reported, the clinical significance of elevated serum prolactin levels is unknown for most patients. An increase in mammary neoplasms has been found in rodents after chronic administration of antipsychotic drugs. Neither clinical studies nor epidemiologic studies conducted to date, however, have shown an association between chronic administration of these drugs and mammary tumorigenesis; the available evidence is considered too limited to be conclusive at this time.

Chromosomal aberrations in spermatocytes and abnormal sperm have been demonstrated in rodents tested with certain antipsychotics.

As with all drugs which exert an anticholinergic effect, and/or cause mydriasis, Prochlorperazine should be used with caution in patients with glaucoma.

Because phenothiazines may interfere with thermoregulatory mechanisms, use with caution in persons who will be exposed to extreme heat.

Phenothiazines can diminish the effect of oral anticoagulants.

Phenothiazines can produce alpha-adrenergic blockade.

Thiazide diuretics may accentuate the orthostatic hypotension that may occur with phenothiazines.

Antihypertensive effects of guanethidine and related compounds may be counteracted when phenothiazines are used concomitantly.

Concomitant administration of propranolol with phenothiazines results in increased plasma levels of both drugs.

Phenothiazines may lower the convulsive threshold; dosage adjustments of anticonvulsants may be necessary. Potentiation of anticonvulsant effects does not occur. However, it has been reported that phenothiazines may interfere with the metabolism of phenytoin and thus precipitate phenytoin toxicity.

The presence of phenothiazines may produce false-positive phenylketonuria (PKU) test results.

Long-Term Therapy

Given the likelihood that some patients exposed chronically to antipsychotics will develop tardive dyskinesia, it is advised that all patients in whom chronic use is contemplated be given, if possible, full information about this risk. The decision to inform patients and/or their guardians must obviously take into account the clinical circumstances and the competency of the patient to understand the information provided.

To lessen the likelihood of adverse reactions related to cumulative drug effect, patients with a history of long-term therapy with Prochlorperazine and/or other antipsychotics should be evaluated periodically to decide whether the maintenance dosage could be lowered or drug therapy discontinued.

Children with acute illnesses (e.g., chickenpox, CNS infections, measles, gastroenteritis) or dehydration seem to be much more susceptible to neuromuscular reactions, particularly dystonias, than are adults. In such patients, the drug should be used only under close supervision.

Drugs which lower the seizure threshold, including phenothiazine derivatives, should not be used with metrizamide. As with other phenothiazine derivatives, Prochlorperazine should be discontinued at least 48 hours before myelography, should not be resumed for at least 24 hours postprocedure, and should not be used for the control of nausea and vomiting occurring either prior to myelography with metrizamide or postprocedure.

Geriatric Use

Clinical studies of Prochlorperazine did not include sufficient numbers of subjects aged 65 and over to determine whether elderly subjects respond differently from younger subjects. Geriatric patients are more sensitive to the side effects of antipsychotics, including Prochlorperazine. These adverse events include hypotension, anticholinergic effects (such as urinary retention, constipation, and confusion), and neuromuscular reactions (such as parkinsonism and tardive dyskinesia) (see PRECAUTIONS and ADVERSE REACTIONS). Also, postmarketing safety experience suggests that the incidence of agranulocytosis may be higher in geriatric patients compared to younger individuals who received Prochlorperazine. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy (see DOSAGE AND ADMINISTRATION).

(proe klor PER a zeen)

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Solution, Injection, as edisylate [strength expressed as base]:

Generic: 5 mg/mL (2 mL, 10 mL [DSC])

Suppository, Rectal:

Compazine: 25 mg (12 ea [DSC])

Compro: 25 mg (12 ea)

Generic: 25 mg (1 ea, 12 ea, 1000 ea)

Tablet, Oral, as maleate [strength expressed as base]:

Compazine: 5 mg [DSC], 10 mg [DSC]

Generic: 5 mg, 10 mg

Prochlorperazine is a piperazine phenothiazine antipsychotic which blocks postsynaptic mesolimbic dopaminergic D1 and D2 receptors in the brain, including the chemoreceptor trigger zone; exhibits a strong alpha-adrenergic and anticholinergic blocking effect and depresses the release of hypothalamic and hypophyseal hormones; believed to depress the reticular activating system, thus affecting basal metabolism, body temperature, wakefulness, vasomotor tone and emesis

Distribution

Vd: 1400 to 1548 L (Taylor 1987)

Metabolism

Primarily hepatic; N-desmethyl prochlorperazine (major active metabolite)

Excretion

Mainly in feces

Oral: 30 to 40 minutes; IM: 10 to 20 minutes; Rectal: ~60 minutes; Peak antiemetic effect: IV: 30 to 60 minutes

Known hypersensitivity to phenothiazines; coma or presence of large amounts of CNS depressants (eg, alcohol, opioids, barbiturates); postoperative management of nausea/vomiting following pediatric surgery; use in infants and children <2 years or <9 kg; pediatric conditions for which dosage has not been established

Documentation of allergenic cross-reactivity for phenothiazines is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.

Canadian labeling: Additional contraindications (not in the US labeling): Presence of circulatory collapse; severe cardiovascular disorders; altered state of consciousness; concomitant use of high dose hypnotics; severe depression; presence of blood dyscrasias, hepatic or renal impairment, or pheochromocytoma; suspected or established subcortical brain damage with or without hypothalamic damage

There are no dosage adjustments provided in the manufacturer’s labeling.

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience anxiety, constipation, dry mouth, or fatigue. Have patient report immediately to prescriber signs of infection, signs of liver problems (dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or jaundice), abnormal movements, twitching, change in balance, difficulty speaking, difficulty swallowing, severe dizziness, passing out, angina, tachycardia, abnormal heartbeat, confusion, mood changes, agitation, seizures, tremors, difficulty moving, rigidity, drooling, swelling of arms or legs, vision changes, bruising, bleeding, urinary retention, severe loss of strength and energy, enlarged breasts, nipple discharge, sexual dysfunction, amenorrhea, signs of neuroleptic malignant syndrome (fever, muscle cramps or stiffness, dizziness, severe headache, confusion, change in thinking, tachycardia, abnormal heartbeat, or sweating a lot), or signs of tardive dyskinesia (unable to control body movements; tongue, face, mouth, or jaw sticking out; mouth puckering; or puffing cheeks) (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.