DIETHYLCARBAMAZINE CITRATE

Chemistry - A piperazine derivative, diethylcarbamazine citrate (DEC) occurs as a white, slightlyhygroscopic, crystalline powder that is either odorless or has a slight odor and a melting point ofapproximately 138°C. It is very soluble in water and slightly soluble (1 gram in 35 ml) in alcohol.

Storage, Stability, Compatibility

Unless otherwise specified by the manufacturer, diethylcar-bamazine products should be stored in tight containers at room temperature and protected fromlight.

Pharmacology - DIETHYLCARBAMAZINE CITRATE

The exact mechanism of how DEC exerts in its anti-filaricidal (early larval stagesof D. immitis) and anti-nematodal effects is not clearly understood. It is believed that DEC acts onthe parasite's nervous system in a nicotinic-like fashion, thereby paralyzing it.

Uses, Indications

DEC is approved (depending on product) for use for the prophylaxis ofheartworm disease (D. immitis), and/or the treatment of ascariasis in dogs. The drug is also used inferrets and zoo animals susceptible to heartworm. DEC is used in dogs at higher dosages asalternative therapy for several other parasites (see Dosage section below). Some products may belabeled for use in cats to treat ascarid infections.
In the U.K., DEC is used as an injectable product to control parasitic bronchitis (Dictyocaulusviviparous) in sheep and cattle.
In humans, DEC is indicated as a filaricidal for the treatment of Wucheria bancrofti, Brugiamalayi, Loa loa and Onchocerca volvulus.

Pharmacokinetics - DIETHYLCARBAMAZINE CITRATE

DEC is rapidly absorbed after oral administration, with peak serum levelsoccurring in about 3 hours. The drug is distributed to all tissues and organs except fat. DEC israpidly metabolized and is primarily excreted in the urine (70% of a dose within 24 hours) asmetabolites or unchanged drug (10-25% of a dose).

Contraindications, Precautions, Reproductive Safety

Diethylcarbamazine is contraindicated indogs with microfilaria, as a shock-like reaction can occur in dogs with microfilaria who are treatedwith DEC. This effect may only be seen in 0.3 - 5% of dogs, but the potential seriousness of thereaction precludes its use in all dogs with microfilaria. Dogs cleared of adult worms andmicrofilaria may be started on DEC therapy for prophylaxis. Microfilaria detected in dogs whohave undergone aldulticide and microfilaricide therapy and are receiving DEC prophylaxis, shouldhave the DEC stopped until existing microfilaria are eliminated.
DEC has been reported to cause infertility problems in male dogs, but these reports are rare.
Controlled studies have not found any adverse effects on semen volume, pH, sperm counts ormotility.
DEC alone is reportedly safe to use in pregnant dogs throughout the gestational period.

Adverse Effects, Warnings

When used at recommended doses for heartworm prophylaxis, adverse effects are very uncommon for DEC. Some dogs develop diarrhea or vomiting while on thedrug, which may necessitate discontinuation. GI effects are more predominant when used at higherdosages for the treatment of ascarids or other susceptible parasites. Giving with food or soon aftereating may alleviate GI disturbances. Case reports of fixed drug eruptions after DEC have also beenreported in dogs.
In microfilaria positive dogs who receive DEC, an anaphylactoid reaction can be seen within 20minutes of dosing. Systems affected or symptoms seen may include GI (salivation, diarrhea, emesis), CNS (depression, ataxia, prostration, lethargy), shock (pale mucous membranes, weakpulses, tachycardia, dyspnea), hepatic (increased liver enzymes) or DIC. The reaction generallypeaks within 1-2 hours after the dose and death can occur. Treatment is basically supportive, usingfluid therapy and intravenous corticosteroids.
In addition to the adverse effects above, the following have been reported with combinationproducts that contain DEC: DEC/Styrylpyridium (Styrid® Caricide®): gastroenteritis, teratogenesis, sterilization and thrombocytopenia. DEC/Oxibendazole (Filaribits® Plus) has been implicated incausing periportal hepatitis in dogs.
Overdosage, Acute Toxicity - DEC is considered to be a relatively non-toxic compound, butquantitative data regarding its toxicity was not found. In dogs, large overdoses generally result invomiting or depression. Inducement of vomiting or absorption reduction measures (activatedcharcoal, cathartics) could be considered for very large ingestions. Symptoms, should they occur, should be handled in a supportive manner.

Drug Interactions

If used with diethylcarbamazine, other nicotine-like compounds (e.g., pyrantel, morantel, levamisole) could theoretically enhance the toxic effects of each other; usewith DEC only with intensified monitoring.