Diethylcarbamazine citrate

391.42

391.195465

216-696-6

OS1Z389K8S

756735|152050|80513

2811

DTXSID4045555

White, crystalline powder

2933595960

159

1.1718 (rough estimate)

141-143 °C

516.39°C (rough estimate)

116.6ºC

1.6500 (estimate)

H2O: almost transparency;Very soluble in water, soluble in ethanol (96 per cent), practically insoluble in acetone.

-20°C Freezer

LD50 orally in rats: 1.38 g/kg (Harned)

Odorless or slight odor

Bitter acid taste

144.6 Ų [M+H]+ [CCS Type: TW, Method: calibrated with polyalanine and drug standards]

Slightly hygroscopic|A 6.29% w/v solution is iso-osmotic with serum.

No rapid reaction with air. No rapid reaction with water.

Alcohols and Polyols

III

6.1(b)

UN 2811 6.1/PG 2

3

22-26-23

22-36/37/39-45

TL1225000

T+,T

The product /as tablets/ is stable even under conditions of high temp and humidity.

P260-P301 + P312 + P330-P304 + P340 + P310-P403 + P233

H302-H330

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

When heated to decomposition, it emits toxic fumes of nitrogen oxides. Avoid decomposing heat. (EPA, 1998)

|Danger|H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]|P260, P264, P270, P271, P284, P301+P312, P304+P340, P310, P320, P330, P403+P233, P405, and P501|Aggregated GHS information provided by 39 companies from 1 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Excerpt from ERG Guide 154 [Substances - Toxic and/or Corrosive (Non-Combustible)]: SMALL FIRE: Dry chemical, CO2 or water spray. LARGE FIRE: Dry chemical, CO2, alcohol-resistant foam or water spray. Move containers from fire area if you can do it without risk. Dike fire-control water for later disposal; do not scatter the material. FIRE INVOLVING TANKS OR CAR/TRAILER LOADS: Fight fire from maximum distance or use unmanned hose holders or monitor nozzles. Do not get water inside containers. Cool containers with flooding quantities of water until well after fire is out. Withdraw immediately in case of rising sound from venting safety devices or discoloration of tank. ALWAYS stay away from tanks engulfed in fire. (ERG, 2016)

Excerpt from ERG Guide 154 [Substances - Toxic and/or Corrosive (Non-Combustible)]: As an immediate precautionary measure, isolate spill or leak area in all directions for at least 50 meters (150 feet) for liquids and at least 25 meters (75 feet) for solids. SPILL: Increase, in the downwind direction, as necessary, the isolation distance shown above. FIRE: If tank, rail car or tank truck is involved in a fire, ISOLATE for 800 meters (1/2 mile) in all directions; also, consider initial evacuation for 800 meters (1/2 mile) in all directions. (ERG, 2016)

(Non-Specific -- Drugs, n.o.s.) Shut off ignition sources; no flares, smoking or flames in hazard area. Keep combustibles (wood, paper, oil, etc.) away from spilled material. Do not touch spilled material. Small spills: take up with sand or other noncombustible absorbent material and place into containers for later disposal. Large spills: dike far ahead of spill for later disposal. Keep unnecessary people away; isolate hazard area and deny entry. Stay upwind; keep out of low areas. (EPA, 1998)

For emergency situations, wear a positive pressure, pressure-demand, full facepiece self-contained breathing apparatus (SCBA) or pressure- demand supplied air respirator with escape SCBA and a fully-encapsulating, chemical resistant suit. (EPA, 1998)

LD50 Rat oral 1.38 g/kg

Filaricides; Lipoxygenase Inhibitors|Dietylcarbamazine citrate is usually admin by mouth as tablets. ... It has also been given by intramuscular injection.|For mass treatment /against microfilariae of Wucereria bancrofti and Wuchereria malayi/ with the objective of reducing microfilaremia to subinfective levels for mosquitoes, the dose is 2 mg/kg, three times daily after meals, for 7 days for treatment directed toward possible cure, this dosage regimen is carried out for 10 to 30 days. ... For practical purposes, an adequate amount seems to be a total dose of about 72 mg/kg of the citrate salt.|For /treatment against Loa loa microfilariae/ a dose of 2 mg/kg should be given 3 times daily after meals for 2 to 3 weeks. If repeated courses are required to produce cure, they should be separated by periods of 3 to 4 weeks.|For more Therapeutic Uses (Complete) data for DIETHYLCARBAMAZINE CITRATE (16 total), please visit the HSDB record page.

There are no contraindications to the use of diethylcarbamazine, other than the fact that low doses should be used for initial therapy, especially in onchocerciasis and infection due to Loa loa (to minimize adverse reactions to destruction of the parasites).|Special care should be taken in using diethylcarbamazine in areas where both onchocerciasis and loaiasis occur. /Diethylcarbamazine/|In patients infected with Onchocerca volvulus or Wuchereria malayi, and to a lesser extent in those infected with Wuchereria bancrofti and Loa loa, the initial systemic reactions provoked by the massive destruction of microfilariae, or both during treatment may be severs. In such cases the dosage should be lowered or the drug stopped temporarily. Relief of these symptoms in heavily infected individuals may be afforded by pretreatment with corticosteroids, for example, dexamethasone (2 to 4 mg twice daily).|... use of diethylcarbamazine in microfilariae-positive dogs, is strictly contraindicated. ... The AVMA Council on Veterinary Services advises that all previously treated heartworm cases should be checked 3 months after the dog is started on diethylcarbamazine. If microfilariae are detected, the prophylactic program must be stopped until existing microfilariae are eliminated.|For more Drug Warnings (Complete) data for DIETHYLCARBAMAZINE CITRATE (6 total), please visit the HSDB record page.

Pharmacological agents destructive to nematodes in the superfamily Filarioidea. (See all compounds classified as Filaricides.)|Compounds that bind to and inhibit that enzymatic activity of LIPOXYGENASES. Included under this category are inhibitors that are specific for lipoxygenase subtypes and act to reduce the production of LEUKOTRIENES. (See all compounds classified as Lipoxygenase Inhibitors.)

Diethylcarbamazine is readily absorbed from the gastrointestinal tract. After a single oral dose of 200 to 400 mg, the concentration in plasma peaks in 1 to 2 hours ... Excretion is nearly all urinary, & more than 70% of the drug appears as metabolites. The compound is distributed almost completely throughout all body compartments with the exception of fat. Little accumulation occurs when repeated doses are given. /Diethylcarbamazine/

Only 10-25% of the drug is excreted unchanged; the remainder is excreted as one of four known metabolites, all of which contain the intact piperazine ring.

... the plasma half-life /in man/ is about 8 hr after a 200 mg dose and 12 hr after an 800 mg dose.

The drug has two types of action on susceptible microfilariae. The first is to decrease the muscular activity and eventually immobilize the organisms; this may result from a hyerpolarizing effect of the piperazine moiety, and it causes dislocation of the parasites from their normal habitat in the host. The second action is to produce alterations in the microfilarial surface membranes, thereby rendering them more susceptible to destruction by host defense mechanisms. There is definite evidence that diethylcarbamazine kills adult worms of Loa loa and presumptive evidence that it kills adult Wuchereria bancrofti and Wuchereria malayi. However, it has little action against adult Onchocerca volvulus. The mechanism of the filaricidal action of diethylcarbamazine is unknown. /Diethylcarbamazine/|It is postulated that in naturally infected animals, diethylcarbamazine somehow promotes the combination of antigen and antibody on the surface of serotonin-rich platelets. Serotonin is released from damaged platelets, which dramatically increases vascular permeability and leads to shock. This generally but not always occurs in dogs with a high microfilaremia.|Diethylcarbamazine causes rapid disappearance of microfilariae of Wuchereriia bancrofti, Wuchereria malayi, and Loa loa from the blood of man. The drug causes microfilariae of Onchlcerca volvulus to disappear from the skin but does not kill microfilariae in nodules that contain the adult (female) worms. It does not affect the microfilariae of Wuchereria bancrofti in a hydrocele, despite penetration into the fluid.

(Non-Specific -- Drugs, n.o.s.) May be fatal if inhaled, swallowed or absorbed through skin. Contact may cause burns to skin and eyes. Fire may produce irritating or poisonous gases. Runoff from fire control or dilution water may cause pollution. The average adult man tolerates a single dose of 1.5 gm without ill effects. (EPA, 1998)

Warning: Effects may be delayed up to 16 hours. Caution is advised. Signs and Symptoms of Diethylcarbamazine Citrate Exposure: Signs and symptoms of acute diethylcarbamazine citrate exposure may include the following: headache, nausea, vomiting, weakness, tachycardia (rapid pulse), hypotension, rapid breathing, mild fever, amd skin rash. Muscle tremors, weakness, and convulsions may also occur. An allergic reaction may occur about 16 hours after the initial exposure. Emergency Life-Support Procedures: Acute exposure to diethylcarbamazine citrate may require decontamination and life support for the victims. Emergency personnel should wear protective clothing appropriate to the type and degree of contamination. Air-purifying or supplied-air respiratory equipment should also be worn, as necessary. Rescue vehicles should carry supplies such as plastic sheeting and disposable plastic bags to assist in preventing spread of contamination. Inhalation Exposure: 1. Move victims to fresh air. Emergency personnel should avoid self-exposure to diethylcarbamazine citrate. 2. Evaluate vital signs including pulse and respiratory rate, and note any trauma. If no pulse is detected, provide CPR. If not breathing, provide artificial respiration. If breathing is labored, administer oxygen or other respiratory support. 3. Obtain authorization and/or further instructions from the local hospital for administration of an antidote or performance of other invasive procedures. 4. Transport to a health care facility. Dermal/Eye Exposure: 1. Remove victims from exposure. Emergency personnel should avoid self-exposure to diethylcarbamazine citrate. 2. Evaluate vital signs including pulse and respiratory rate, and note any trauma. If no pulse is detected, provide CPR. If not breathing, provide artificial respiration. If breathing is labored, administer oxygen or other respiratory support. 3. Remove and isolate contaminated clothing as soon as possible. 4. If eye exposure has occurred, eyes must be flushed with lukewarm water for at least 15 minutes. 5. Wash exposed skin areas thoroughly with water. 6. Obtain authorization and/or further instructions from the local hospital for administration of an antidote or performance of other invasive procedures. 7. Transport to a health care facility. Ingestion Exposure: 1. Evaluate vital signs including pulse and respiratory rate, and note any trauma. If no pulse is detected, provide CPR. If not breathing, provide artificial respiration. If breathing is labored, administer oxygen or other respiratory support. 2. Obtain authorization and/or further instructions from the local hospital for administration of an antidote or performance of other invasive procedures. 3. Vomiting may be induced with syrup of Ipecac. If elapsed time since ingestion of diethylcarbamazine citrate is unknown or suspected to be greater than 30 minutes, do not induce vomiting and proceed to Step 4. Ipecac should not be administered to children under 6 months of age.Warning: Syrup of Ipecac should be administered only if victims are alert, have an active gag-reflex, and show no signs of impending seizure or coma. If ANY uncertainty exists, proceed to Step 4.The following dosages of Ipecac are recommended: children up to 1 year old, 10 mL (1/3 oz); children 1 to 12 years old, 15 mL (1/2 oz); adults, 30 mL (1 oz). Ambulate (walk) the victims and give large quantities of water. If vomiting has not occurred after 15 minutes, Ipecac may be readministered. Continue to ambulate and give water to the victims. If vomiting has not occurred within 15 minutes after second administration of Ipecac, administer activated charcoal. 4. Activated charcoal may be administered if victims are conscious and alert. Use 15 to 30 g (1/2 to 1 oz) for children, 50 to 100 g (1-3/4 to 3-1/2 oz) for adults, with 125 to 250 mL (1/2 to 1 cup) of water. 5. Promote excretion by administering a saline cathartic or sorbitol to conscious and alert victims. Children require 15 to 30 g (1/2 to 1 oz) of cathartic; 50 to 100 g (1-3/4 to 3 1/2 oz) is recommended for adults. 6. Transport to a health care facility. (EPA, 1998)

Untoward direct reactions to diethylcarbamazine ... are not severe and usually disappear within a few days despite continuation of therapy. These include headache, general malaise, weakness, joint pains, anorexia, nausea, & vomiting. Other adverse effects result directly or indirectly from destruction of the parasites. These are especially severe in patients heavily infected with Onchocerce volvulus. In Wuchereria bancrofti or Loa loa infections, reactions are usually milder, although the drug may induce severe encephalitis in Loa loa. /Diethylcarbamazine/|In patients with onchocerciasis, there is usually a typical reaction within 16 hours after the first oral dose. This consists in intense itching & skin rashes, enlargement & tenderness of the inguinal lymph nodes, sometimes a fine papular rash, hyperpyrexia, tachycardia, and headache. These symtoms persist for 3 to 7 days and then subside, after which quite high doses can be tolerated. Ocular complications include limbitis, punctate keratitis, uveitis, and atrophy of the retinal pigment epithelium. Nodular swellings may occur along the course of the lymphatics, & there is often an accompanying lymphadenitis. This reaction also subsides within a few days. Almost all patients receiving therapy exhibit a leukocytosis, first evident on the second day, reaching its peak on the fourth or fifth day, & gradually subsiding over a period of a few weeks. Reversible proteinuria may occur, and the eosinophilia frequently observed in patients with filariasis can be intensified by drug therapy. /Diethylcarbamazine/|Four cases of persistent proteinuria and 3 cases of transient proteinuria are reported among 20 patients treated with diethylcarbamazine citrate, 2% topically or 50 mg orally.

Carbamazine

The drug is marketed as the dicitrate salt.|Vet: Some preperations (Styrid-Carcicide) contain not only diethylcarbamazine citrate but also as ingredient effective against the 3rd stage (infective) larvae of hookworms.|Vet: Diethylcarbamazine is prepared as either a syrup, powder, or tablet (chewable or nonchewable) and sold under several trade names.|Grade: USP|Diethylcarbamazine citrate tablets contain not less than 98.0% and not more than 100.5% of C10-H21-N3-0.C6-H8-0 calculated on the anhydrous basis.

1-Piperazinecarboxamide, N,N-diethyl-4-methyl-, 2-hydroxy-1,2,3-propanetricarboxylate (1:1): ACTIVE

Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients|Animal Drugs -> FDA Approved Animal Drug Products (Green Book) -> Active Ingredients