Usage
Diethylcarbamazine citrate is an anthelmintic medication primarily prescribed for treating filarial infections, including:
- Lymphatic filariasis: Caused by Wuchereria bancrofti, Brugia malayi, or Brugia timori.
- Loiasis: Caused by Loa loa (eye worm).
- Tropical pulmonary eosinophilia: Caused by filarial parasites.
- Toxocariasis: In some regions.
- Mass drug administration (MDA): For lymphatic filariasis elimination programs.
Pharmacological Classification: Anthelmintic.
Mechanism of Action: Diethylcarbamazine immobilizes microfilariae and renders them more susceptible to destruction by the host’s immune system. The exact mechanism is complex and not fully understood but likely involves several processes:
- Platelet-mediated triggering of antigen release from microfilariae.
- Altered prostaglandin metabolism in the parasite, leading to immobilization via cholinergic muscle receptor inhibition.
- Disruption of microtubule formation within the parasite.
- Changes in the helminth surface membrane, increasing susceptibility to immune attack.
Alternate Names
- DEC
- Hetrazan (brand name)
- Banocide (brand name)
- Notezine (brand name)
How It Works
Pharmacodynamics: Diethylcarbamazine primarily affects microfilariae, making them easier for the host’s immune system to eliminate. In some filarial species, it also impacts adult worms.
Pharmacokinetics:
- Absorption: Readily absorbed from the gastrointestinal tract after oral administration.
- Distribution: Widely distributed throughout body tissues.
- Metabolism: Partially metabolized to diethylcarbamazine N-oxide in the liver.
- Elimination: Primarily excreted in the urine, both as unchanged drug and metabolite. A smaller portion is eliminated in feces. Half-life is approximately 8-12 hours.
Mode of Action: (See Mechanism of Action above). It is important to note that in Onchocerca volvulus (river blindness), the drug primarily acts on microfilariae, causing their death which can lead to a severe inflammatory reaction known as the Mazzotti reaction. This can cause serious ocular side effects, thus the drug is generally contraindicated in onchocerciasis.
Receptor binding, enzyme inhibition, or neurotransmitter modulation: Current evidence suggests interference with arachidonic acid metabolism, impacting prostaglandin and leukotriene production within the parasite.
Elimination pathways: Mainly renal excretion (urine), partially as the unchanged drug and as the N-oxide metabolite. A minor portion is eliminated through feces.
Dosage
Standard Dosage
Adults:
The dosage is generally weight-based, starting at a lower dose and gradually increasing over several days to minimize adverse reactions.
- Lymphatic Filariasis: Start with 1 mg/kg on day 1, increasing to 6 mg/kg/day (divided into three doses) for 12-14 days. In MDA programs, a single annual dose of 6 mg/kg is common.
- Loiasis: Start with a low dose (e.g., 50 mg) and gradually increase over 3 days to a target of 6-9 mg/kg/day (divided into three doses) for 21 days. Microfilarial load assessment is crucial before treatment (See Precautions). Prophylaxis: 300 mg weekly.
- Tropical Pulmonary Eosinophilia: 6 mg/kg/day for 14-21 days.
- Toxocariasis: Start with 1 mg/kg twice daily, increasing to 6 mg/kg/day (divided doses) for 21 days.
Children:
- Children typically receive similar weight-based dosing regimens as adults but under close supervision. Some sources suggest reducing the dose by half for children under 10 in the treatment of lymphatic filariasis.
- For loiasis, weight-based dosing (8-10 mg/kg/day in three divided doses) is used for 21 days, but microfilarial load must be assessed before treatment.
Special Cases:
- Elderly Patients: Exercise caution due to potential age-related decline in organ function.
- Patients with Renal Impairment: Dose adjustments are necessary due to reduced clearance; the extent depends on the degree of impairment.
- Patients with Hepatic Dysfunction: While information is limited, caution is advised.
- Patients with Comorbid Conditions: Pre-existing cardiac conditions necessitate careful monitoring.
Clinical Use Cases
Diethylcarbamazine is not typically used in clinical settings such as intubation, surgical procedures, mechanical ventilation, or the intensive care unit. It is primarily indicated for the specific parasitic infections mentioned previously. In emergency situations involving these infections, standard dosing protocols apply.
Dosage Adjustments
(See Special Cases under Standard Dosage above) Dosage adjustments should be individualized considering renal function, potential drug interactions, and patient tolerance.
Side Effects
Common Side Effects
- Fever
- Headache
- Nausea, vomiting, diarrhea
- Dizziness, drowsiness
- Fatigue
- Lymphadenopathy
- Skin rash
- Itching
Rare but Serious Side Effects
- Encephalopathy (particularly in patients with loiasis and high microfilarial loads)
- Severe allergic reactions
- Ocular complications (in onchocerciasis, if present as a co-infection)
- Hypotension
- Mazzotti reaction
Long-Term Effects
Visual impairment can be a long-term consequence of the Mazzotti reaction, primarily in patients with co-existing onchocerciasis.
Adverse Drug Reactions (ADR)
Severe hypersensitivity reactions, encephalopathy, and ocular damage (if untreated) represent clinically significant ADRs requiring immediate intervention.
Contraindications
- Hypersensitivity to diethylcarbamazine.
- Pregnancy (unless absolutely necessary).
- Breastfeeding (due to unknown risk to the infant).
- Infants, the elderly, and debilitated patients (generally excluded from MDA programs).
- Onchocerciasis (due to the risk of the Mazzotti reaction).
- Severe cardiac or renal disease.
Drug Interactions
Limited information available. Consult drug interaction databases for the most up-to-date details. Potential interactions may exist with drugs metabolized by the liver, although specific CYP450 interactions are not well documented.
Pregnancy and Breastfeeding
- Pregnancy: Contraindicated unless the benefit outweighs the risk. The FDA category is not assigned, and limited human data are available, but animal studies have shown harm.
- Breastfeeding: Not recommended due to unknown excretion in breast milk and potential risk to the newborn.
Drug Profile Summary
(See previous sections for detailed information)
Popular Combinations
Diethylcarbamazine is often co-administered with albendazole in MDA programs for lymphatic filariasis, as this combination enhances efficacy. Albendazole targets adult worms, while diethylcarbamazine is primarily microfilaricidal.
Precautions
(See previous sections for more detailed information)
- Pre-screening for Loa loa microfilaremia is essential before initiating treatment for other filarial infections. High Loa Loa microfilarial loads can trigger severe encephalopathy.
- Patients with onchocerciasis should not receive DEC.
- Monitor patients carefully during the initial days of treatment for adverse reactions.
- Consider concomitant corticosteroid use during treatment for loiasis to reduce inflammation and severity of reactions.
- Renal impairment may necessitate dosage adjustments.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Diethylcarbamazine?
A: Dosage is weight-based and varies depending on the infection. See the Dosage section for specific guidelines for adults, children, and special populations.
Q2: What are the most common side effects of Diethylcarbamazine?
A: Common side effects include fever, headache, gastrointestinal disturbances, dizziness, fatigue, and skin reactions.
Q3: Is Diethylcarbamazine safe during pregnancy and breastfeeding?
A: Diethylcarbamazine is generally contraindicated during pregnancy and breastfeeding. Consult a specialist if absolutely necessary.
Q4: How does Diethylcarbamazine work against filarial parasites?
A: Diethylcarbamazine immobilizes microfilariae and makes them more vulnerable to the host’s immune system. The precise mechanism is complex and multifactorial.
Q5: What is the Mazzotti reaction, and why is it important?
A: The Mazzotti reaction is a severe inflammatory response that can occur in individuals with onchocerciasis treated with Diethylcarbamazine. It can cause severe adverse effects, including ocular complications and systemic symptoms. Diethylcarbamazine is therefore contraindicated in patients with onchocerciasis.
Q6: What are the contraindications for the use of Diethylcarbamazine?
A: Contraindications include hypersensitivity, onchocerciasis, pregnancy, breastfeeding, severe cardiac or renal disease, and in infants, the elderly and debilitated.
Q7: What precautions are necessary when prescribing Diethylcarbamazine for loiasis?
A: Carefully assess the patient’s microfilarial load before treatment, as high loads increase the risk of severe encephalopathy. Consider using albendazole or apheresis to reduce very high loads before initiating diethylcarbamazine. Monitor the patient closely for adverse reactions.
Q8: Are there any significant drug interactions with Diethylcarbamazine?
A: Limited data are available on drug interactions. Consult a comprehensive drug interaction database for the latest information.
Q9: What is the role of Diethylcarbamazine in Mass Drug Administration programs?
A: It is often used in combination with albendazole in MDA programs for eliminating lymphatic filariasis. The combination enhances efficacy.
Q10: What is the difference between weight-based and age-based dosing for Diethylcarbamazine?
A: Weight-based dosing is generally preferred and takes into account individual variations in drug metabolism. Age-based dosing is sometimes used in MDA programs for simplicity, but weight-based dosing provides more precise drug levels.
