PBZ-SR
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PBZ-SR (PBZ-SR).
Antihistamine; H1-receptor antagonist that competes with histamine for binding at H1 receptor sites, thereby preventing histamine-mediated allergic responses.
| Metabolism | Hepatic metabolism via hydroxylation and glucuronide conjugation; major metabolites include triprolidine metabolites. |
| Excretion | Primarily renal excretion (80-90% as unchanged drug) via glomerular filtration and tubular secretion. Biliary/fecal excretion accounts for approximately 5-10%. |
| Half-life | Terminal elimination half-life is approximately 4-6 hours in adults with normal renal function; clinically relevant dosing every 4-6 hours is recommended. |
| Protein binding | Approximately 85-90% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Volume of distribution is 1.0-2.0 L/kg, indicating extensive tissue penetration and distribution into total body water. |
| Bioavailability | Oral bioavailability is 25-35% due to first-pass hepatic metabolism; intravenous and intramuscular routes provide complete bioavailability (100%). |
| Onset of Action | Oral: 30-60 minutes; Intramuscular: 10-20 minutes; Intravenous: 1-5 minutes. |
| Duration of Action | Duration of action is 4-6 hours for oral and intramuscular routes; intravenous duration may be slightly shorter at 3-4 hours due to rapid redistribution. |
| Molecular Weight | 403.5 |
100-200 mg orally every 12 hours; maximum 400 mg/day.
| Dosage form | TABLET, EXTENDED RELEASE |
| Renal impairment | GFR 30-50 mL/min: reduce dose by 50%; GFR <30 mL/min: not recommended. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: not recommended. |
| Pediatric use | 2-5 mg/kg/day divided every 12 hours; maximum 200 mg/day. |
| Geriatric use | Start at 50 mg twice daily; titrate cautiously due to increased anticholinergic sensitivity. |
| 1st trimester | Avoid use due to potential teratogenicity; limited human data, animal studies show risk. |
| 2nd trimester | Avoid use; may cause fetal harm; consider alternatives. |
| 3rd trimester | Avoid near term; risk of neonatal complications (e.g., respiratory depression, withdrawal). |
Clinical note
Comprehensive clinical and safety monograph for PBZ-SR (PBZ-SR).
| Placental transfer | Crosses placenta; detected in fetal plasma at concentrations similar to maternal. |
| Breastfeeding | Excreted in human milk; potential for serious adverse reactions in nursing infants. Decision to discontinue nursing or drug based on importance to mother. |
| Lactation Rating |
■ FDA Black Box Warning
None.
| Serious Effects |
Hypersensitivity to PBZ-SR or any componentMAOI use within 14 daysNarrow-angle glaucomaSymptomatic prostatic hypertrophyUrinary retentionSevere liver disease
| Precautions | Sedation and CNS depression; avoid driving or operating machinery., Concurrent use with CNS depressants may enhance sedation., Use with caution in patients with glaucoma, prostatic hyperplasia, urinary retention, or asthma., Elderly patients may be more sensitive to anticholinergic effects and sedation. |
| Food/Dietary | Grapefruit juice may increase prochlorperazine serum concentrations via CYP3A4 inhibition. Avoid excessive caffeine consumption as it may worsen extrapyramidal symptoms. High-fat meals may reduce absorption of PBZ-SR; take consistently with or without food. |
Loading safety data…
| L4 (Possibly Hazardous) |
| Teratogenic Risk | Tripelennamine, the active ingredient in PBZ-SR, is an H1 antihistamine. Animal studies have not demonstrated teratogenic effects. Human data: limited case reports show no consistent pattern of major malformations. First trimester: theoretical risk, but data insufficient to establish safety. Second and third trimesters: no known fetal risks; however, use near term may cause neonatal irritability or respiratory depression. Overall, tripelennamine is considered low risk but should be used only if clearly needed. |
| Fetal Monitoring | No specific maternal-fetal monitoring required beyond routine prenatal care. Observe for maternal sedation or hypotension. In neonates exposed near term, monitor for respiratory depression, irritability, or feeding difficulties. |
| Fertility Effects | No known adverse effects on human fertility reported in animal or human studies. Tripelennamine does not alter hormonal profiles or interfere with conception based on limited data. |
| Clinical Pearls | PBZ-SR (prochlorperazine) is a phenothiazine antiemetic with significant extrapyramidal side effect risk, especially in elderly and young patients. Use lowest effective dose for shortest duration. Avoid in patients with Parkinson's disease or suspected Reye's syndrome. Monitor for QT prolongation, neuroleptic malignant syndrome (NMS), and tardive dyskinesia. An extrapyramidal symptom (EPS) like acute dystonia can be treated with diphenhydramine 25-50 mg IM/IV or benztropine 1-2 mg IV/IM. Potentiates CNS depressants including alcohol and opioids. |
| Patient Advice | Take exactly as prescribed; do not crush or chew the sustained-release tablet. · Avoid driving or operating heavy machinery until you know how this drug affects you. · Report any involuntary muscle movements, stiffness, or restlessness to your doctor immediately. · Avoid alcohol and other central nervous system depressants (sedatives, tranquilizers, opioids). · Rise slowly from sitting or lying positions to prevent dizziness or fainting. · Do not stop taking suddenly without consulting your doctor; gradual dose reduction may be needed. |