Prochlorperazine Edisylate

PROCHLORPERAZINE EDISYLATE- prochlorperazine edisylate injection
Mylan Institutional LLC

DESCRIPTION

Prochlorperazine edisylate, 2-Chloro-10-[3-(4-methyl-1-piperazinyl)propyl]phenothiazine 1,2- ethanedisulfonate (1:1), has the following structural formula:

C₂₀ H₂₄ ClN₃ S C₂ H₆ O₆ S₂ MW 564.14

Prochlorperazine Edisylate Injection, USP an antiemetic and antipsychotic, is a sterile solution intended for intramuscular or intravenous administration.

Each mL contains Prochlorperazine Edisylate, USP equivalent to Prochlorperazine 5 mg, monobasic sodium phosphate monohydrate 5 mg, sodium tartrate dihydrate 12 mg, saccharin sodium 0.9 mg and benzyl alcohol 7.5 mg in water for injection. pH 4.2 to 6.2.

CLINICAL PHARMACOLOGY

Prochlorperazine is a propylpiperazine derivative of phenothiazine. Like other phenothiazines, it exerts an antiemetic effect through a depressant action on the chemoreceptor trigger zone. It also has a clinically useful antipsychotic effect. Following intramuscular administration of prochlorperazine edisylate, the drug has an onset of action within ten to twenty minutes and a duration of action of three to four hours.

INDICATIONS AND USAGE

To control severe nausea and vomiting. For the treatment of schizophrenia.

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

CONTRAINDICATIONS

Do not use in patients with known hypersensitivity to phenothiazines.

Do not use in comatose states or in the presence of large amounts of central nervous system depressants (alcohol, barbiturates, narcotics, etc.).

Do not use in pediatric surgery.

Do not use in pediatric patients under 2 years of age or under 20 lbs. Do not use in children for conditions for which dosage has not been established.

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 edisylate injection 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. 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 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.

Falls

Prochlorperazine Edisylate Injection may cause somnolence, postural hypotension, motor and sensory instability, which may lead to falls and, consequently, fractures or other injuries. For patients with diseases, conditions, or medications that could exacerbate these effects, complete fall risk assessments when initiating antipsychotic treatment and recurrently for patients on long-term antipsychotic therapy.