Prochlorperazine, a phenothiazine derivative is designated chemically as 2-Chloro -10- [3-(4-methyl-1-piperazinyl)propyl]phenothiazine with the following structural formula: Each rectal suppository contains 25 mg prochlorperazine with glycerin, glyceryl monostearate, hydrogenated coconut oil fatty acids, hydrogenated palm kernel oil fatty acids.
Prochlorperazine is a propylpiperazine derivative of phenothiazine. Like other phenothiazines, it exerts an antiemetic effect through a depressant action on the chemoreceptor trigger zone.
For Adults, Prochlorperazine Suppositories, USP 25 mg in boxes of 12 and 1000 as follows:Box of 12 NDC 0713-0135-12Box of 1000 NDC 0713-0135-10 Rx only Storage: Store at 20-25��C (68-77��F) [See USP Controlled Room Temperature]. Do not remove from foil until ready to use. Manufactured by: G&W Laboratories, Inc., S. Plainfield, N.J. 07080
The antiemetic action of prochlorperazine may mask the 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 . When prochlorperazine is used with cancer chemotherapeutic drugs, vomiting as a sign of the 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. If hypotension occurs after parenteral or oral dosing, place patient in head-low position with legs raised. If a vasoconstrictor is required, norepinephrine bitartrate and phenylephrine hydrochloride 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 post-surgical 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. Neuroleptic 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 prescribing of these drugs in 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 neuroleptic drugs. Neither clinical 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 treated with certain neuroleptics. 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 phenyketonuria (PKU) test results. Long-Term Therapy: Given the likelihood that some patients exposed chronically to neuroleptics 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 neuroleptics should be evaluated periodically to decide whether the maintenance dosage could be lowered or drug therapy discontinued. Children with acute illnesses (e.g., chicken pox, C.N.S. 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 derivates, 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.
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 anti-parkinsonism drugs, barbiturates, or diphenhydramine. 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, norepinephrine bitartrate and phenylephrine hydrochloride are most suitable. Other pressor agents, including epinephrine, are not recommended because phenothiazine derivatives may reverse the usual elevating action of these agents and causea further lowering of blood pressure. Limited experience indicates that phenothiazines are not dialyzable.
Increased Mortality in Elderly Patients with Dementia-Related PsychosisElderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Prochlorperazine Suppositories, USP is not approved for the treatment of patients with dementia-related psychosis . 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 neuroleptic (anti-psychotic) 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 differin 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 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 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. 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.