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Chapter: Basic & Clinical Pharmacology - Clinical Pharmacology of the Antihelminthic Drugs

Diethylcarbamazine Citrate

Diethylcarbamazine is a drug of choice in the treatment of filari-asis, loiasis, and tropical eosinophilia. It has been replaced by ivermectin for the treatment of onchocerciasis.

DIETHYLCARBAMAZINE CITRATE

Diethylcarbamazine is a drug of choice in the treatment of filari-asis, loiasis, and tropical eosinophilia. It has been replaced by ivermectin for the treatment of onchocerciasis.

Basic Pharmacology

Diethylcarbamazine, a synthetic piperazine derivative, is marketed as a citrate salt. It is rapidly absorbed from the gastrointestinaltract; after a 0.5 mg/kg dose, peak plasma levels are reached within 1–2 hours. The plasma half-life is 2–3 hours in the presence of acidic urine but about 10 hours if the urine is alkaline, a Henderson-Hasselbalch trapping effect . The drug rapidly equilibrates with all tissues except fat. It is excreted, prin-cipally in the urine, as unchanged drug and the N-oxide metabo-lite. Dosage may have to be reduced in patients with persistent urinary alkalosis or renal impairment.

Diethylcarbamazine immobilizes microfilariae and alters their surface structure, displacing them from tissues and making them more susceptible to destruction by host defense mechanisms. The mode of action against adult worms is unknown.

Clinical Uses

The drug should be taken after meals.

A. Wuchereria bancrofti, Brugia malayi, Brugia timori, and Loa loa

 

Diethylcarbamazine is the drug of choice for treatment of infections with these parasites because of its efficacy and lack of serious toxicity. Microfilariae of all species are rapidly killed; adult parasites are killed more slowly, often requiring several courses of treatment. The drug is highly effective against adult L loa. The extent to which W bancrofti and B malayi adults are killed is not known, but after appropriate therapy microfilariae do not reappear in the majority of patients.

These infections are treated for 2 or (for L loa) 3 weeks, with initial low doses to reduce the incidence of allergic reactions to dying microfilariae. This regimen is 50 mg (1 mg/kg in children) on day 1, three 50 mg doses on day 2, three 100 mg doses (2 mg/kg in children) on day 3, and then 2 mg/kg three times daily to complete the 2–3 week course.

Antihistamines may be given for the first few days of therapy to limit allergic reactions, and corticosteroids should be started and doses of diethylcarbamazine lowered or interrupted if severe reactions occur. Cures may require several courses of treatment. For patients with high L loa worm burdens (more than 2500 cir-culating parasites/mL), strategies to decrease risks of severe toxicity include apheresis, if available, to remove microfilariae before treat-ment with diethylcarbamazine or therapy with albendazole, which is slower acting and better tolerated, before therapy with diethyl-carbamazine or ivermectin.

 

Diethylcarbamazine may also be used for chemoprophylaxis (300 mg weekly or 300 mg on 3 successive days each month for loiasis; 50 mg monthly for bancroftian and Malayan filariasis).

B. Other Uses

For tropical eosinophilia, diethylcarbamazine is given orally at a dosage of 2 mg/kg three times daily for 7 days. Diethylcarbamazine is effective in Mansonella streptocerca infections, since it kills both adults and microfilariae. Limited information suggests that the drug is not effective, however, against adult M ozzardi or M per-stans and that it has limited activity against microfilariae of theseparasites. An important application of diethylcarbamazine has been mass treatment to reduce the prevalence of W bancrofti infec-tion, generally in combination with ivermectin or albendazole.This strategy has led to excellent progress in disease control in a number of countries.

Adverse Reactions, Contraindications, & Cautions

Reactions to diethylcarbamazine, which are generally mild and transient, include headache, malaise, anorexia, weakness, nausea, vomiting, and dizziness. Adverse effects also occur as a result of the release of proteins from dying microfilariae or adult worms. Reactions are particularly severe with onchocerciasis, but diethyl-carbamazine is no longer commonly used for this infection, because ivermectin is equally efficacious and less toxic. Reactions to dying microfilariae are usually mild in W bancrofti, more intense in B malayi, and occasionally severe in L loa infections. Reactions include fever, malaise, papular rash, headache, gastroin-testinal symptoms, cough, chest pain, and muscle or joint pain. Leukocytosis is common. Eosinophilia may increase with treat-ment. Proteinuria may also occur. Symptoms are most likely to occur in patients with heavy loads of microfilariae. Retinal hemor-rhages and, rarely, encephalopathy have been described.

Between the third and twelfth days of treatment, local reactions may occur in the vicinity of dying adult or immature worms. These include lymphangitis with localized swellings in W bancrofti and B malayi, small wheals in the skin in L loa, and flat papules in M streptocerca infections. Patients with attacks of lymphangitis dueto W bancrofti or B malayi should be treated during a quiescent period between attacks.Caution is advised when using diethylcarbamazine in patients with hypertension or renal disease.


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