Chemistry - Piperazine occurs as a white, crystalline powder that may have a slight odor. It is soluble in water and alcohol. Piperazine is available commercially in a variety of salts, including citrate, adipate, phosphate, hexahydrate and dihydrochloride. Each salt contains a variable amount of piperazine (base): adipate (37%), chloride (48%), citrate (35%), dihydrochloride (50-53%), hexahydrate (44%), phosphate (42%) and sulfate (46%).
Storage/Stability/Compatibility - Unless otherwise specified by the manufacturer, piperazine products should be stored at room temperature (15-30°C).
Pharmacology - Piperazine is thought to exert “curare-like” effects on susceptible nematodes, thereby paralyzing or narcotizing the worm and allowing it to be passed out with the feces. The neuromuscular blocking effect is believed to be caused by blocking acetylcholine at the myoneural junction. In ascarids, succinic acid production is also inhibited.
Uses/Indications - Piperazine is used for the treatment of ascarids in dogs, cats, horses, swine and poultry. Piperazine is considered to be safe to use in animals with concurrent gastroenteritis and during pregnancy.
Pharmacokinetics - Piperazine and its salts are reportedly readily absorbed from the proximal sections of the GI tract and the drug is metabolized and excreted by the kidneys. Absorptive, distribution and elimination kinetics on individual species were not located.
Contraindications/Precautions - Piperazine should be considered contraindicated in patients with chronic liver or kidney disease, and in patients with gastrointestinal hypomotility. There is some evidence in man, that piperazine may provoke seizures in patients with a seizure history or with renal disease when given in high dosages.
If used in horses with heavy infestations of P. equorum, rupture or blockage of intestines is possible due to the rapid death and detachment of the worm.
Adverse Effects/Warnings - Adverse effects are uncommon at recommended doses, but diarrhea, emesis and ataxia may be noted in dogs or cats. Horses and foals generally tolerate the drug quite well, even at high dosage rates, but a transient softening of the feces may be seen. Other adverse effects have been seen at toxic dosages, refer to the Overdosage section below for more information.
Overdosage - Acute massive overdosage can lead to paralysis and death, but the drug is generally considered to have a wide margin of safety. The oral LD50 of piperazine adipate in mice is 11.4 g/kg.
In cats, adverse effects occur within 24 hours after a toxic dose is ingested. Emesis, weakness, dyspnea, muscular fasiculations of ears, whiskers, tail and eyes, rear limb ataxia, hypersalivation, depression, dehydration, head-pressing, positional nystagmus and slowed pupillary responses have all been described after a toxic ingestion. Many of these effects may also be seen in dogs after toxic piperazine ingestions.
Treatment is symptomatic and supportive. If ingestion was recent, use of activated charcoal and a cathartic has been suggested. Intravenous fluid therapy and keeping the animal in a quiet, dark place is also recommended. Recovery generally takes place within 3-4 days.
Drug Interactions - Although data conflicts, piperazine and chlorpromazine may precipitate seizures if used concomitantly. Piperazine and pyrantel/morantel have antagonistic modes of action and should generally not be used together. The use of purgatives (laxatives) with piperazine is not recommended as the drug may be eliminated before its full efficacy is established.
Drug/Laboratory Interactions - Piperazine can have an effect on uric acid blood levels, but references conflict with regard to the effect. Both falsely high and low values have been reported. Use results cautiously.
Doses - Caution: Piperazine is available in several salts that contain varying amounts of piperazine base (see Chemistry above). Many of the doses listed below do not specify what salt (if any) is used in the dosage calculations. If the dose is in question, refer to the actual product information for the product you are using.
Horses: There are combination products available for use in horses (see Dosage Forms/Preparations section) that contain piperazine that have increased efficacy against nematodes and other helminths. Refer to the individual products’ package insert for more information.
a) 110 mg/kg (base) PO; repeat in 3-4 weeks. Retreating at 10 week intervals for P. equorum infections in young animals is recommended. (Roberson 1988b)
b) 200 mg/kg PO. Maximum of 80 grams in adults, 60 grams in yearlings, and 30 grams in foals. (Brander, Pugh, and Bywater 1982)
Monitoring Parameters -1) Clinical and/or laboratory efficacy 2) Adverse effects
Client Information - Clients should be instructed to administer only the amount prescribed and to relate any serious adverse effects to the veterinarian.
Dosage Forms/Preparations/Approval Status/Withdrawal Times -
Piperazine Dihydrochloride tablets equivalent to 50 mg, or 250 mg base. Pipa-Tabs® (Vet-A-Mix); (OTC) Approved for use in dogs and cats.
Additional products and combination products may be available for a variety of species.
Human-Approved Products: None
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