Note: Dosages expressed as diethylcarbamazine citrate; some products may alternatively list dosing according to diethylcarbamazine (base). The ratio of diethylcarbamazine citrate to diethylcarbamazine (base) is approximately 2:1.
Loiasis:
Treatment: Oral: 8 to 10 mg/kg/day in 3 divided doses for 21 days; for patients with symptomatic loiasis and microfilarial loads ≥8,000 microfilariae/mL, apheresis or albendazole treatment prior to treatment with diethylcarbamazine is recommended (Ref). Note: For patients with microfilaria in the blood, some clinicians recommend the following dose-escalating regimen: 50 mg as a single dose on day 1; 50 mg 3 times daily on day 2; 100 mg 3 times daily on day 3; 9 mg/kg/day in 3 divided doses on day 4 to end of treatment course (Ref). Repeat courses of treatment may be needed to achieve cure (Ref).
Prophylaxis: Oral: 300 mg once weekly; continue as long as exposure occurs (Ref).
Lymphatic filariasis ( W. bancrofti, B. malayi, B. timori) : Oral: 6 mg/kg/day for 1 or 12 days (14 to 21 days in patients with tropical pulmonary eosinophilia); daily dose may be given as a single dose or in 3 divided doses (Ref). Note: For patients with microfilaria in the blood, some clinicians recommend the following dose-escalating regimen: 50 mg as a single dose on day 1; 50 mg 3 times daily on day 2; 100 mg 3 times daily on day 3; 6 mg/kg/day in 3 divided doses on day 4 to end of treatment course (Ref).
Reduce dose in renal impairment (no specific adjustment is provided) (Ref).
Refer to adult dosing.
(For additional information see "Diethylcarbamazine (United States: Available via CDC drug service investigational drug [IND] protocol only): Pediatric drug information")
Note: Dosages expressed as diethylcarbamazine citrate; some products may alternatively list dosing according to diethylcarbamazine (base). The ratio of diethylcarbamazine citrate to diethylcarbamazine (base) is approximately 2:1.
Loiasis, treatment:
Note: Patients with microfilarial loads ≥8,000 microfilariae/mL should receive apheresis or treatment with albendazole prior to treatment with diethylcarbamazine (Ref).
Children and Adolescents: Oral: 8 to 10 mg/kg/day in 3 divided doses for 21 days; repeat courses of treatment may be needed to achieve cure (Ref). Note: For patients with microfilaria in the blood, some clinicians recommend starting with a lower dosage (eg, 50 mg/day) with gradual increase over 3 days to 9 mg/kg/day in 3 divided doses on day 4 through the end of the 21-day treatment course (Ref).
Lymphatic filariasis:
Children ≥18 months and Adolescents: Oral: 6 mg/kg as a single dose or 6 mg/kg/day in 3 divided doses for 12 days; in patients with tropical pulmonary eosinophilia, treat for 14 to 21 days (Ref). Note: For patients with microfilaria in the blood, some clinicians recommend starting with a lower dosage (eg, 50 mg/day) with gradual increase over 3 days to 6 mg/kg/day in 3 divided doses on day 4 through the end of the treatment course (Ref).
There are no recommendations specific for pediatric patients. Based on pharmacokinetics and experience in adult patients, dosage should be reduced in renal impairment. Dose reductions may be needed in patients with diets that promote urinary alkalinization; elimination half-life is prolonged and AUC is increased in alkaline urine (Ref).
There are no recommendations for patients with hepatic impairment (has not been studied).
The following adverse drug reactions are derived from product labeling unless otherwise specified.
Frequency not defined:
Cardiovascular: Tachycardia
Dermatologic: Urticaria
Gastrointestinal: Abdominal pain, decreased appetite, diarrhea, nausea, vomiting
Genitourinary: Proteinuria
Hematologic & oncologic: Lymphadenitis
Hypersensitivity: Hypersensitivity reaction
Nervous system: Asthenia, coma, dizziness, drowsiness, encephalitis (allergic), encephalopathy, fatigue, headache, lassitude, lethargy, meningoencephalitis (helminthic), vertigo
Neuromuscular & skeletal: Myalgia
Ophthalmic: Conjunctivitis, corneal edema, eye pain, increased intraocular pressure, iridocyclitis, lacrimation, optic neuritis, photophobia, punctate keratitis, visual field defect
Respiratory: Asthma
Miscellaneous: Fever, Mazzotti reaction
Patients with onchocerciasis (CDC 2020a; CDC 2020b).
Concerns related to adverse effects:
• Encephalopathy: When treating loiasis, encephalopathy (sometimes fatal), and other severe neurologic adverse reactions may occur; risk is related to the microfilarial load. Microfilarial load must be tested prior to treatment. Use caution if microfilarial load >2,500 microfilariae/mL; patients with microfilarial loads ≥8,000 microfilariae/mL should have the load reduced through apheresis or treatment with albendazole before initiation of treatment with diethylcarbamazine. Corticosteroid use and/or slow dose escalation has not been shown to decrease the risk of fatal encephalopathy (CDC 2020a; CDC 2020b).
• Inflammatory reactions: Use in patients with onchocerciasis may precipitate Mazzotti reaction (pruritus, fever, arthralgia). Inflammatory response occurring in the cornea and retina can result in permanent visual damage (McCarthy 2015). Use is contraindicated in patients with onchocerciasis; possibility of co-infection with onchocerciasis should be excluded prior to initiation of treatment with diethylcarbamazine (CDC 2020b).
• Skin reactions: In patients treated for loiasis, some symptoms of loiasis (eg, Calabar swelling, pruritus) may increase briefly during treatment; concomitant use of antihistamines and corticosteroids during the first week of treatment may decrease these symptoms (CDC 2020a).
Disease-related concerns:
• Cardiac disorders: Use with caution in patients with cardiac disorders (WHO [Stuart 2009]).
• Renal impairment: Use with caution; dosage reduction recommended (Adjepon-Yamoah 1982).
Other warnings/precaution:
• Alkaline urine: Elimination half-life is prolonged and AUC is increased in alkaline urine; dose reductions may be needed in patients with diets that promote urinary alkalinization (Adjepon-Yamoah 1982).
Diethylcarbamazine is not commercially available in the US; it is available for the treatment of lymphatic filariasis and tropical pulmonary eosinophilia, and for treatment/prevention of loiasis through the Centers for Disease Control (CDC) Drug Service for patients that meet the eligibility criteria in the Investigational New Drug (IND) protocol. For more information, contact the CDC at 404-718-4745, parasites@cdc.gov or visit https://www.cdc.gov/laboratory/drugservice/formulary.html.
Oral: Administer after meals (Ref).
Oral: Administer after meals (Ref).
Loiasis: Treatment and prophylaxis of loiasis caused by Loa loa.
Lymphatic filariasis: Treatment of lymphatic filariasis caused by Wuchereria bancrofti, Brugia malayi, or Brugia timori.
None known.
There are no known significant interactions.
Outcome data following inadvertent exposure to diethylcarbamazine during pregnancy are limited (Weil 2019; WHO 2006). Use of diethylcarbamazine during pregnancy is not recommended (de Silva 1997; WHO 2006). Filarial infection (W. bancrofti, Loa loa) can be transmitted from mother to fetus during pregnancy (Bal 2015; Momb-Ngoma 2015); eradication of maternal infection prior to pregnancy or delaying treatment until after delivery is recommended (Bal 2015; WHO [Stuart 2009]). Patients who are pregnant should avoid exposure if traveling to infected areas (McGovern 2007).
It is not known if diethylcarbamazine is present in breast milk; breastfeeding is not recommended.
Renal function at baseline and periodically during treatment; in patients with loiasis, measure microfilarial load prior to treatment; patients with microfilarial loads ≥8,000 microfilariae/mL treated with albendazole to reduce microfilarial load should have close, frequent monitoring of microfilarial load to confirm reduction before initiation of treatment with diethylcarbamazine (CDC 2020a).
Exact mechanism of action is unknown. Proposed mechanisms include platelet-mediated triggering of release of excretory antigen from microfilariae; alterations of prostaglandin metabolism in microfilariae and host endothelial cells that leads to immobilization by inhibition of parasite cholinergic muscle receptors; disruption of microtubule formation; and alterations in helminth surface membranes that result in enhanced killing by the host immune system (deSilva 1997; McCarthy 2015).
Absorption: Well absorbed (de Silva 1997).
Protein binding: Not significant (McCarthy 2015).
Half-life elimination: 10 to 12 hours (McCarthy 2015).
Time to peak: 1 to 2 hours (de Silva 1997).
Excretion: Urine (~50% as unchanged drug; ~10% as metabolite); feces (~10%) (de Silva 1997).
Altered kidney function: Elimination half-life is prolonged and urinary excretion is reduced (Adjepon-Yamoah 1982).
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