PROKETAZINE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PROKETAZINE (PROKETAZINE).
Phenothiazine neuroleptic with central antidopaminergic and anticholinergic effects; blocks dopamine D2 receptors in the chemoreceptor trigger zone and hypothalamus, producing antiemetic and antipsychotic activity.
| Metabolism | Hepatic via CYP2D6 and other cytochrome P450 enzymes. |
| Excretion | Primarily renal excretion of metabolites; less than 1% excreted unchanged in urine. Biliary/fecal elimination accounts for approximately 20% of total clearance. |
| Half-life | Terminal elimination half-life is 15-20 hours in healthy adults; may be prolonged in elderly or hepatic impairment. |
| Protein binding | Approximately 90-95% bound to plasma proteins, primarily albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Volume of distribution is 20-30 L/kg, indicating extensive tissue distribution and high lipophilicity. |
| Bioavailability | Oral bioavailability is 30-40% due to extensive first-pass metabolism. IM bioavailability is approximately 70%. |
| Onset of Action | Intravenous: 2-3 minutes; intramuscular: 10-15 minutes; oral: 30-60 minutes. |
| Duration of Action | Duration of antipsychotic effect is 6-8 hours after oral dosing; sedative effects may persist for 12-24 hours. Repeat dosing may lead to accumulation. |
| Molecular Weight | 326.9 |
25 mg intramuscularly every 6-8 hours; maximum 100 mg per day.
| Dosage form | CONCENTRATE |
| Renal impairment | GFR 30-50 mL/min: reduce dose by 25%; GFR <30 mL/min: reduce dose by 50% and extend interval to every 12 hours. |
| Liver impairment | Child-Pugh Class A: no adjustment; Class B: reduce dose by 50%; Class C: avoid use. |
| Pediatric use | 0.5-1 mg/kg intramuscularly every 6-8 hours; maximum 50 mg per day for children <12 years. |
| Geriatric use | Initial dose 12.5 mg intramuscularly; maximum 50 mg per day; monitor for anticholinergic effects and sedation. |
| 1st trimester | Avoid in first trimester unless benefits outweigh risks; may be associated with congenital malformations (limited data). |
| 2nd trimester | Use with caution; no specific evidence of fetal harm but limited data. |
| 3rd trimester | Avoid near term due to risk of neonatal respiratory depression, hypotonia, and withdrawal symptoms. |
Clinical note
Comprehensive clinical and safety monograph for PROKETAZINE (PROKETAZINE).
| Placental transfer | Crosses the placenta; degree not well quantified but expected due to molecular weight. |
| Breastfeeding | Excreted into breast milk in small amounts; monitor infant for sedation and feeding difficulties; use only if clearly needed. |
| Lactation Rating |
■ FDA Black Box Warning
Increased risk of death in elderly patients with dementia-related psychosis; not approved for dementia-related psychosis.
| Serious Effects |
Hypersensitivity to proketazine or any excipientComatose statesCentral nervous system depressionBone marrow suppressionSevere hepatic impairment
| Precautions | May cause QT prolongation, neuroleptic malignant syndrome, tardive dyskinesia, hypotension, and increased risk of falls. Use with caution in patients with cardiovascular disease, seizures, or hepatic impairment. |
| Food/Dietary | Avoid grapefruit juice as it may inhibit metabolism and increase toxicity. Avoid high-tyramine foods (aged cheese, cured meats, fermented products) due to risk of hypertensive crisis if used with MAOIs. |
Loading safety data…
| L3 (Moderately Safe) |
| Teratogenic Risk | PROKETAZINE (prochlorperazine) is classified as FDA Pregnancy Category C. First trimester: Limited human data; animal studies show teratogenic effects at high doses. Second/third trimesters: Possible extrapyramidal symptoms and neonatal withdrawal in newborns after maternal use near term. Use only if benefit outweighs risk. |
| Fetal Monitoring | Monitor maternal blood pressure, heart rate, and signs of extrapyramidal reactions. Fetal monitoring: Ultrasonography for growth and development if used during pregnancy. In newborns, monitor for respiratory depression, hypotonia, and withdrawal symptoms. |
| Fertility Effects | Prochlorperazine may elevate prolactin levels, potentially causing galactorrhea, amenorrhea, and reduced fertility in females. In males, effects on spermatogenesis are not well-documented but possible due to dopamine blockade. Effects are reversible upon discontinuation. |
| Clinical Pearls | Monitor for extrapyramidal symptoms, especially in elderly and pediatric patients. Proketazine may cause significant hypotension; avoid rapid IV administration. Contraindicated in patients with bone marrow suppression or severe hepatic impairment. |
| Patient Advice | Avoid alcohol and CNS depressants as they may increase sedation. · Report any involuntary muscle movements or stiffness immediately. · Rise slowly from sitting or lying to prevent dizziness. · May cause dry mouth; use sugar-free gum or candy. · Do not discontinue abruptly without consulting prescriber. |