Diethylcarbamazine citrate (N, N-diethyl-4-methyl-1-piperazine carboxamide dihydrogen citrate or DEC) is derived from the anthelminthic agent piperazine.
Diethylcarbamazine is the drug of choice for treatment of lymphatic filariasis, caused by the parasites Wuchereria bancrofti, Brugia malayi, and of loaiais caused by the filarial parasite Loa loa. A summary of the effects of DEC on geohelminths is shown in Table 1.
Proposed mechanisms of action include platelet-mediated triggering of the release of excretory antigen from microfilariae, with killing involving free radicals, drug-induced alteration of prostaglandin metabolism in microfilariae and/or in host endothelial cells, leading to immobilization of microfilariae on endothelial surfaces and adherence and killing by host platelets and granulocytes and inhibition of microtubule polymerization.
No mechanism has been suggested
Diethylcarbamazine is well absorbed following oral administration with peak plasma concentrations reached within 1-2 hours. The elimination half life ranges from 10-12 hours. If the urine is alkalinized, renal excretion of unchanged drug is prevented and the half life of the drug increases.
While the standard regimen for treatment of Bancroftian filariasis is traditionally 6 mg/kg/day, (generally divided into 3 doses for increased tolerability) for 12 days, to reach a total dose of 72 mg/kg, recent studies have shown that single doses of diethylcarbamazine (DEC) have the same long-term (1-year) effect in decreasing microfilaraemia as the formerly-recommended 12-day regimens of DEC. More importantly, the use of single doses of 2 drugs administered concurrently (optimally albendazole with DEC or ivermectin) is 99% effective in removing microfilariae from the blood for a full year after treatment. It is this level of treatment effectiveness that has made feasible the new efforts to eliminate lymphatic filariasis.
No data exist regarding the safety or dose modification of the drug in pregnancy.
Adverse reactions to diethylcarbamazine may be due either to a direct effect of the drug, or occur as a response to the pharmacodynamic effect of the drug on the worm. The latter, frequently referred to as the Mazzotti reaction, is best recognized in individuals with onchocerciasis, but a less severe form may be seen in other filarial infections. Recent work has defined the role of the pro-inflammatory cytokines interleukin-6 (IL-6) and tumour necrosis factor (TNF) in the pathogenesis of this reaction.
No significant drug interactions have been reported with diethylcarbamazine.