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

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.

NOTE ON INJECTION: For intramuscular administration, inject deeply into the upper, outer quadrant of the buttock. Subcutaneous administration is not advisable because of local irritation.

Prochlorperazine Edisylate Injection, USP 5 mg/mL is a colorless to slightly yellowish solution and supplied as follows: 10 mg/2 mL single-dose prefilled syringes (NDC 0641-6225-01).  Packaged as a carton of 10 x 2 mL single-dose prefilled syringes (NDC 0641-6225-10).

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.

Prochlorperazine edisylate, 2-Chloro-10-[3-(4-methyl-1-piperazinyl)propyl]phenothiazine 1,2-ethanedisulfonate (1:1), has the following structural formula: Prochlorperazine Edisylate Injection, USP an antiemetic and antipsychotic, is a sterile solution intended for intramuscular or intravenous administration. Each mL contains prochlorperazine 5 mg as the edisylate, monobasic sodium phosphate monohydrate 5 mg, sodium tartrate dihydrate 12 mg and saccharin sodium 0.9 mg in Water for Injection. pH 4.2-6.2.

Neonates exposed to antipsychotic drugs, during the 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 edisylate should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

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.

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 of 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 PRECAUTIONS and Dystonia ).

Drowsiness, dizziness, amenorrhea, blurred vision, skin reactions and hypotension may occur. Neuroleptic Malignant Syndrome (NMS) has been reported in association with antipsychotic drugs (see WARNINGS ). Cholestatic jaundice has occurred. If fever with grippe-like symptoms occurs, appropriate liver studies should be conducted. If tests indicate an abnormality, stop treatment. There have been a few observations of fatty changes in the livers of patients who have died while receiving the drug. No causal relationship has been established. Leukopenia and agranulocytosis have occurred. Warn patients to report the sudden appearance of sore throat or other signs of infection. If white blood cell and differential counts indicate leukocyte depression, stop treatment and start antibiotic and other suitable therapy.

(See also ADVERSE REACTIONS .)

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.

  Rx only

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 agranulocytsosis 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 ).

PROTECT FROM LIGHT . Store in the box until ready to use. Discard if markedly discolored. Discard unused portion. Store at 20˚ to 25˚C (68˚ to 77˚F); excursions permitted to 15º to 30ºC (59º to 86ºF) [see USP Controlled Room Temperature]. To report SUSPECTED ADVERSE REACTIONS, contact Hikma Pharmaceuticals USA Inc. at 1-877-845-0689, or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . For Product Inquiry call 1-877-845-0689.   Manufactured by : Hikma Pharmaceuticals USA Inc. Berkeley Heights, NJ 07922 Revised November 2022 462-961-00

NDC 0641- 6225 -01     Rx only 2 mL Single-Dose Prefilled Syringe Prochlorperazine  Edisylate Injection, USP 10 mg per 2 mL  (5 mg/mL) For Deep IM or IV Use Only - Not for SC Use PROTECT FROM LIGHT NDC 0641- 6225 -10       Rx only Prochlorperazine  Edisylate Injection, USP 10 mg per 2 mL (5 mg/mL) For Deep Intramuscular or Intravenous Use ONLY Not for Subcutaneous Use PROTECT FROM LIGHT. Keep covered in carton until time of use. Discard contents if markedly discolored. 10 x 2 mL Single-Dose Prefilled Syringes

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

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.

NOTE ON INJECTION: For intramuscular administration, inject deeply into the upper, outer quadrant of the buttock. Subcutaneous administration is not advisable because of local irritation.

Prochlorperazine Edisylate Injection, USP 5 mg/mL is a colorless to slightly yellowish solution and supplied as follows: 10 mg/2 mL single-dose prefilled syringes (NDC 0641-6225-01).  Packaged as a carton of 10 x 2 mL single-dose prefilled syringes (NDC 0641-6225-10).

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.

Neonates exposed to antipsychotic drugs, during the 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 edisylate should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

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.

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 of 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 PRECAUTIONS and Dystonia ).

Drowsiness, dizziness, amenorrhea, blurred vision, skin reactions and hypotension may occur. Neuroleptic Malignant Syndrome (NMS) has been reported in association with antipsychotic drugs (see WARNINGS ). Cholestatic jaundice has occurred. If fever with grippe-like symptoms occurs, appropriate liver studies should be conducted. If tests indicate an abnormality, stop treatment. There have been a few observations of fatty changes in the livers of patients who have died while receiving the drug. No causal relationship has been established. Leukopenia and agranulocytosis have occurred. Warn patients to report the sudden appearance of sore throat or other signs of infection. If white blood cell and differential counts indicate leukocyte depression, stop treatment and start antibiotic and other suitable therapy.

(See also ADVERSE REACTIONS .)

Prochlorperazine edisylate, 2-Chloro-10-[3-(4-methyl-1-piperazinyl)propyl]phenothiazine 1,2-ethanedisulfonate (1:1), has the following structural formula: Prochlorperazine Edisylate Injection, USP an antiemetic and antipsychotic, is a sterile solution intended for intramuscular or intravenous administration. Each mL contains prochlorperazine 5 mg as the edisylate, monobasic sodium phosphate monohydrate 5 mg, sodium tartrate dihydrate 12 mg and saccharin sodium 0.9 mg in Water for Injection. pH 4.2-6.2.

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.

  Rx only

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 agranulocytsosis 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 ).

PROTECT FROM LIGHT . Store in the box until ready to use. Discard if markedly discolored. Discard unused portion. Store at 20˚ to 25˚C (68˚ to 77˚F); excursions permitted to 15º to 30ºC (59º to 86ºF) [see USP Controlled Room Temperature]. To report SUSPECTED ADVERSE REACTIONS, contact Hikma Pharmaceuticals USA Inc. at 1-877-845-0689, or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . For Product Inquiry call 1-877-845-0689.   Manufactured by : Hikma Pharmaceuticals USA Inc. Berkeley Heights, NJ 07922 Revised November 2022 462-961-00

NDC 0641- 6225 -01     Rx only 2 mL Single-Dose Prefilled Syringe Prochlorperazine  Edisylate Injection, USP 10 mg per 2 mL  (5 mg/mL) For Deep IM or IV Use Only - Not for SC Use PROTECT FROM LIGHT NDC 0641- 6225 -10       Rx only Prochlorperazine  Edisylate Injection, USP 10 mg per 2 mL (5 mg/mL) For Deep Intramuscular or Intravenous Use ONLY Not for Subcutaneous Use PROTECT FROM LIGHT. Keep covered in carton until time of use. Discard contents if markedly discolored. 10 x 2 mL Single-Dose Prefilled Syringes