Prochlorperazine 10 MG Oral Tablet

WARNINGS

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.

Prochlorperazine maleate 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 use 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 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 antipsychotic drug treatment, which patients are likely to develop the syndrome.

Whether antipsychotic 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 antipsychotic 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of tardive dyskinesia, although the syndrome may remit, partially or completely, if antipsychotic drug treatment is withdrawn.

Antipsychotic drug 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, antipsychotic drugs should be prescribed in a manner that is most likely to minimize the occurrence of tardive dyskinesia especially in the elderly.

Chronic antipsychotic treatment should generally be reserved for patients who suffer from a chronic illness that, 1) is known to respond to antipsychotic 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 antipsychotics, 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 syndrome complex sometimes 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 inadequately 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 systems (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.

An encephalopathic syndrome (characterized by weakness, lethargy, fever, tremulousness and confusion, extrapyramidal symptoms, leukocytosis, elevated serum enzymes, BUN and FBS) has occurred in a few patients treated with lithium plus an antipsychotic.

In some instances, the syndrome was followed by irreversible brain damage.

Because of a possible causal relationship between these events and the concomitant administration of lithium and antipsychotics, patients receiving such combined therapy should be monitored closely for early evidence of neurologic toxicity and treatment discontinued promptly if such signs appear.

This encephalopathic syndrome may be similar to or the same as neuroleptic malignant syndrome (NMS).

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.

Non-teratogenic Effects Neonates exposed to antipsychotic drugs, during third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery.

There have been reports of agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress and feeding disorder in these neonates.

These complications have varied in severity; while in some cases symptoms have been self-limited, in other cases neonates have required intensive care unit support and prolonged hospitalization.

Prochlorperazine Maleate should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

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

Caution should be exercised when prochlorperazine is administered to a nursing woman.

OVERDOSAGE

(See also ADVERSE REACTIONS .

) SYMPTOMS –Primarily involvement of the extrapyramidal mechanism producing some of the dystonic reactions described above.

Symptoms of central nervous system depression to the point of somnolence or coma.

Agitation and restlessness may also occur.

Other possible manifestations include convulsions, EKG changes and cardiac arrhythmias, fever and autonomic reactions such as hypotension, dry mouth and ileus.

TREATMENT–It is important to determine other medications taken by the patient since multiple-dose therapy is common in overdosage situations.

Treatment is essentially symptomatic and supportive.

Early gastric lavage is helpful.

Keep patient under observation and maintain an open airway, since involvement of the extrapyramidal mechanism may produce dysphagia and respiratory difficulty in severe overdosage.

Do not attempt to induce emesis because a dystonic reaction of the head or neck may develop that could result in aspiration of vomitus.

Extrapyramidal symptoms may be treated with antiparkinsonism drugs, barbiturates or Benadryl.

See prescribing information for these products.

Care should be taken to avoid increasing respiratory depression.

If administration of a stimulant is desirable, amphetamine, dextroamphetamine or caffeine with sodium benzoate is recommended.

Stimulants that may cause convulsions (e.g., picrotoxin or pentylenetetrazol) should be avoided.

If hypotension occurs, the standard measures for managing circulatory shock should be initiated.

If it is desirable to administer a vasoconstrictor, Levophed and Neo-Synephrine are most suitable.

Other pressor agents, including epinephrine, are not recommended because phenothiazine derivatives may reverse the usual elevating action of these agents and cause further lowering of blood pressure.

Limited experience indicates that phenothiazines are not dialyzable.

DESCRIPTION

Prochlorperazine is a phenothiazine derivative, present in prochlorperazine tablets as the maleate.

Prochlorperazine maleate is designated chemically as 2-chloro-10-[3-(4- methyl-1 -piperazinyl)propyl] phenothiazine maleate [molecular weight 606.10] and has the following structure Prochlorperazine Maleate is classified as an anti-emetic and antipsychotic agent.

Prochlorperazine maleate is white or pale yellow, practically odorless crystalline powder.

It is practically insoluble in water and in alcohol; slightly soluble in warm chloroform.

Each tablet, for oral administration contains prochlorperazine maleate equivalent to 5 mg or 10 mg of prochlorperazine.

In addition, each tablet contains the following inactive ingredients: D&C yellow no.

10 aluminum lake, FD&C blue no.

2 aluminum lake, FD&C yellow no.

6 aluminum lake, hydroxypropyl methylcellulose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, polyethylene glycol, polysorbate 80, pregelatinized starch, stearic acid and titanium dioxide.

Structure of Prochlorperazine

HOW SUPPLIED

Prochlorperazine Maleate Tablets USP are available in the following strengths and package sizes: 5mg (Chartreuse, round, scored, film-coated, imprinted TL 113) Bottles of 100 NDC 59746-113-06 Bottles of 1000 NDC 59746-113-10 10mg (Chartreuse, round, scored, film-coated, imprinted TL 115) Bottles of 100 NDC 59746-115-06 Bottles of 1000 NDC 59746-115-10

INDICATIONS AND USAGE

For control of severe nausea and vomiting.

For the treatment of schizophrenia.

Prochlorperazine is effective for the short-term treatment of generalized non-psychotic anxiety.

However, prochlorperazine is not the first drug to be used in therapy for most patients with non-psychotic anxiety, because certain risks associated with its use are not shared by common alternative treatments (e.g., benzodiazepines).

When used in the treatment of non-psychotic anxiety, prochlorperazine should not be administered at doses of more than 20 mg per day or for longer than 12 weeks, because the use of prochlorperazine at higher doses or for longer intervals may cause persistent tardive dyskinesia that may prove irreversible (see WARNINGS ).

The effectiveness of prochlorperazine as treatment for non-psychotic anxiety was established in 4-week clinical studies of outpatients with generalized anxiety disorder.

This evidence does not predict that prochlorperazine will be useful in patients with other non-psychotic conditions in which anxiety, or signs that mimic anxiety, are found (e.g., physical illness, organic mental conditions, agitated depression, character pathologies, etc.).

Prochlorperazine has not been shown effective in the management of behavioral complications in patients with mental retardation.

BOXED WARNING

WARNING 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.

Analyses of seventeen placebo-controlled trials (modal duration of 10 weeks), largely in patients taking atypical antipsychotic drugs, revealed a risk of death in drug-treated patients of between 1.6 to 1.7 times the risk of death in placebo-treated patients.

Over the course of a typical 10-week controlled trial, the rate of death in drug-treated patients was about 4.5% compared to a rate of about 2.6% in the placebo group.

Although the causes of death were varied, most of the deaths appeared to be either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature.

Observational studies suggest that, similar to atypical antipsychotic drugs, treatment with conventional antipsychotic drugs may increase mortality.

The extent to which the findings of increased mortality in observational studies may be attributed to the antipsychotic drug as opposed to some characteristic(s) of the patients is not clear.

Prochlorperazine maleate is not approved for the treatment of patients with dementia-related psychosis (see WARNINGS ).

DOSAGE AND ADMINISTRATION

DOSAGE & ADMINISTRATION – ADULTS (For children’s dosage and administration, see below.) Dosage should be increased more gradually in debilitated or emaciated patients.

Elderly Patients: In general, dosages in the lower range are sufficient for most elderly patients.

Since they appear to be more susceptible to hypotension and neuromuscular reac­tions, such patients should be observed closely.

Dosage should be tailored to the individual, response carefully moni­tored and dosage adjusted accordingly.

Dosage should be increased more gradually in elderly patients.

1.To Control Severe Nausea and Vomiting: Adjust dosage to the response of the individual.

Begin with the lowest recommended dosage.

Oral Dosage-Tablets: Usually one 5mg or 10mg tablet 3 or 4 times daily.

Daily dosages above 40 mgs should be used only in resistant cases.

2.In Adult Psychiatric Disorders: Adjust dosage to the response of the individual and according to the severity of the condition.

Begin with the lowest recom­mended dose.

Although response ordinarily is seen within a day or 2, longer treatment is usually required before maximal improvement is seen.

Oral Dosage: Non-Psychotic Anxiety–Usual dosage is 5 mg 3 or4 times daily.

Do not administer in doses of more than 20mg per day or for longer than 12 weeks.

Psychotic Disorders including Schizophrenia –Inrelatively mild conditions, as seen in private psychiatric practice or in out patient clinics, dosage is 5 or 10 mg 3 or 4 times daily.

In moderate to severe conditions, for hospitalized or adequate­ly supervised patients, usual starting dosage is 10 mg 3 or 4 times daily.

Increase dosage gradually until symptoms are con­trolled or side effects become bothersome.

When dosage is increased by small increments every 2 or 3 days, side effects either do not occur or are easily controlled.

Some patients respond satisfactorily on 50 to 75mg daily.

In more severe dis­turbances, optimum dosage is usually 100 to 150mg daily.

–CHILDREN Do not use in pediatric surgery.

Children seem more prone to develop extrapyramidal reac­tions, even on moderate doses.

Therefore, use lowest effec­tive dosage.

Tell parents not to exceed prescribed dosage, since the possibility for adverse reactions increases as dosage rises.

Occasionally the patient may react to the drug with signs of restlessness and excitement; if this occurs, do not administer additional doses.

Take particular precaution in administering the drug to children with acute illnesses or dehydration (see under Dystonias).

1.

Severe Nausea and Vomiting in Children: Prochlorperazine should not be used in pediatric patients under 20 pounds in weight or 2 years of age.

It should not be used in conditions for which children’s dosages have not been established.

Dosage and frequency of administration should be adjusted according to the severity of the symptoms and the response of the patient.

The duration of activity following intra­muscular administration may last up to 12 hours.

Subsequent doses may be given by the same route if necessary.

Oral Dosage: More than 1 day’s therapy is seldom necessary.

Weight Usual Dosage Not to Exceed under 20 lbs not recommended 20 to 29 lbs 2½ mg 1 or 2 times a day 7.5 mg per day 30 to 39 lbs 2½ mg 2 or 3 times a day 10 mg per day 40 to 85 lbs 2½ mg 3 times a day or 5 mg 2 times a day 15 mg per day 2.

Children with schizophrenia: Oral Dosage: For children 2 to 12 years, starting dosage is 2 1 /2 mg 2 or 3 times daily.

Do not give more than 10 mg the first day.

Then increase dosage according to patient’s response.

FOR AGES 2 to 5, total daily dosage usually does not exceed 20mg.

FOR AGES 6 to 12, total daily dosage usually does not exceed 25mg.