Diethylcarbamazine (DEC)
The mechanism of action of DEC is poorly understood. It has no filaricidal effect in vitro, but appears to render microfilariae more susceptible to destruction by host defense mechanisms through effects on the surface membrane [1] and parasite motility [2]. The mechanism of action against adult worms is unknown [1], although some studies have suggested that DEC compromises intracellular processing and transport of certain macromolecules to the plasma membrane [3].
Peak serum levels are achieved in 1–2 hours after a single oral dose and plasma half-life varies from 2–10 hours, depending on the urinary pH. DEC is excreted by both urinary and extra-urinary routes; more than 50% of the oral dose appears in acidic urine as the unchanged drug. Alkalinizing the urine can elevate plasma levels, prolong half-life and increase the therapeutic effect and toxicity of DEC.
• Treatment of lymphatic filariasis*:
• Renal: hematuria, proteinuria.
• Gastrointestinal: abdominal pain, nausea.
• Neurologic (L. loa): headache and, rarely, neuropsychiatric problems, entrapment neuropathy or encephalopathy.
• Skin and soft tissue: rash, subcutaneous nodules, angioedema, urticaria.
• Lymphatic (W. bancrofti and Brugia spp): adenitis, lymphangitis and, rarely, acute lymphedema or hydrocele, scrotal nodules, epididymitis.
• Systemic: fever, headache, malaise, myalgia, arthralgia, orthostatic hypotension.
Onchocerciasis should be excluded in all patients with a consistent exposure history owing to the possibility of severe exacerbations of skin and eye involvement (Mazzotti reaction). DEC should be used with extreme caution in patients with circulating L. loa microfilarial levels >2500/mm3 owing to the potential for life-threatening side effects, including encephalopathy and renal failure. Neither steroids pretreatment nor slow dose escalation prevents these complications.
DEC is not currently licensed for commercial use in the USA, but is available to US-licensed physicians from the CDC under an Investigational New Drug (IND) protocol for treatment of loiasis and lymphatic filariasis and chemoprophylaxis of loiasis.
Dosing recommendations are empiric as no formal studies have been conducted. Consequently, lower doses may be prudent depending on the initial microfilarial load, patient age, weight and/or medical status (e.g. renal disease).
1 Hawking F. Diethylcarbamazine and new compounds for the treatment of filariasis. Adv Pharmacol Chemother. 1979;16:129–194.
2 Langham ME, Kramer TR. The “in vitro” effect of diethylcarbamazine on the motility and survival of Onchocerca volvulus microfilariae. Tropenmed Parasitol. 1980;31:59–66.
3 Spiro RC, Parsons WG, Pery SK, et al. Inhibition of post-translational modification and surface expression of a melanoma-associated chondroitin sulfate proteoglycan by diethylcarbamazine or ammonium chloride. J Biol Chem. 1986;261:1521–1529.
4 Adjepon-Yamoah KK, Edwards G, Breckenridge AM, et al. The effect of renal disease on the pharmacokinetics of diethylcarbamazine in man. Br J Clin Pharm. 1982;13:829–834.
* For patients with microfilariae in the blood, some experts recommend starting with a lower dosage and scaling up: day 1: 50 mg, day 2: 50 mg three times/day, day 3: 100 mg three times/day, day 4–12: 6 mg/kg divided in three doses.