PIPERAZINE CITRATE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PIPERAZINE CITRATE (PIPERAZINE CITRATE).
Piperazine citrate acts as a gamma-aminobutyric acid (GABA) receptor agonist in nematodes, causing hyperpolarization of nerve membranes and flaccid paralysis of the worm, which is then expelled by normal peristalsis. It does not affect mammalian neuromuscular junctions due to differences in GABA receptor sensitivity.
| Metabolism | Piperazine is partially metabolized in the liver via N-methylation and oxidation. Approximately 20-40% of the dose is metabolized, with the remainder excreted unchanged in the urine. The metabolic pathways are not fully characterized, but CYP450 enzymes are minimally involved. |
| Excretion | Primarily renal (60-70% unchanged); biliary/fecal elimination accounts for 10-20% of the dose. |
| Half-life | Terminal elimination half-life: 2-4 hours in patients with normal renal function; may be prolonged in renal impairment. |
| Protein binding | Less than 10% bound to plasma proteins. |
| Volume of Distribution | Vd approximately 0.5-0.6 L/kg, indicating distribution mainly in extracellular fluid. |
| Bioavailability | Oral bioavailability is variable (30-60%) due to first-pass metabolism. |
| Onset of Action | Orally: Onset of anthelmintic effect within 2-4 hours after administration. |
| Duration of Action | Duration of action: Approximately 4-6 hours after a single oral dose; clinical efficacy for ascariasis may persist for 24-48 hours due to worm expulsion. |
| Action Class | Antiprotozoal agents |
| Brand Substitutes | Piperazine Citrate 750mg Syrup, Avizine Syrup, Antepar 750mg Syrup, Piperazine Citrate Syrup |
Adults: 3.5 g orally once daily for 2 days; may repeat after 1 week if needed.
| Dosage form | SYRUP |
| Renal impairment | GFR 10-50 mL/min: reduce dose by 50%; GFR <10 mL/min: contraindicated. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: avoid use. |
| Pediatric use | Children 2-12 years: 75 mg/kg/day (max 3.5 g/day) orally once daily for 2 days. |
| Geriatric use | Use lowest effective dose; monitor for neurotoxicity and renal function; reduce dose if CrCl <50 mL/min. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for PIPERAZINE CITRATE (PIPERAZINE CITRATE).
| Breastfeeding | Excreted in breast milk in small amounts. M/P ratio not established. Use with caution, potential for adverse effects in nursing infant. |
| Teratogenic Risk | No adequate well-controlled studies in pregnant women. Animal studies not available. Potential risk unknown. Avoid use in first trimester unless benefits outweigh risks. |
| Fetal Monitoring |
■ FDA Black Box Warning
None
| Serious Effects |
["Hypersensitivity to piperazine or any component of the formulation","Pre-existing seizure disorders or epilepsy","Renal impairment (risk of neurotoxicity due to reduced clearance)","Concurrent use with pyrantel pamoate (antagonistic effect)"]
| Precautions | ["May cause neurotoxicity (e.g., dizziness, ataxia, seizures) especially in patients with renal impairment or pre-existing neurological disorders","Avoid use in patients with epilepsy or other seizure disorders","Use with caution in patients with hepatic or renal disease","May interfere with urine screening tests for catecholamines, causing false elevations","Concomitant use with pyrantel pamoate is contraindicated due to antagonistic effects"] |
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| Monitor for maternal gastrointestinal disturbances, neurotoxicity; fetal monitoring not standard. |
| Fertility Effects | No known adverse effects on fertility in humans. |