Oxamnichin

1.5

2.24

Pale yellow crystals from isopropanol

Yellow-orange, crystalline solid

1 part in about 3300 parts of water at 27 °C

1.24e-01 g/L

FDA approved drugs -> Active ingredient

FDA approved drugs -> Active ingredient

Antischistosomals and other antitrematode medicines

147-149 °C

147-149 °C

147 - 149 °C

Warning

H302 (97.4%): Harmful if swallowed [Warning Acute toxicity, oral]

P264, P270, P273, P301+P317, P330, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 39 reports by companies from 2 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C. 321-392).

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed drug products, incl oxamniquine, approved on the basis of safety and effectiveness by FDA under sections 505 and 507 of the Federal Food, Drug, and Cosmetic Act. /From the Prescription Drug Product List/

Limited evidence from one study in mice indicates that the antischistosomal activity of oxamniquine and praziquantel may be synergistic against Schistosoma mansoni when the two drugs are administered concomitantly.

The rate and extent of GI absorption of the drug are decreased by the presence of food.

Nervous system effects occur frequently with oxamniquine; however, most of these effects are mild and transient. The most frequent adverse effects of oxamniquine are dizziness, drowsiness, and headache, which occur in about 30-50% of patients receiving the drug. Other less frequent adverse nervous effects ... include behavioral changes, excitation, and hallucinations or distortion of reality. Insomnia, malaise, and reversible amnesia have been reported rarely. EEG abnormalities occur occasionally in patients. ... Generalized seizures, which usually occur within the first few hours ... and generally are associated with EEG changes, have been observed rarely in patients receiving the drug, particularly in those with a history of seizure disorders.

GI effects of oxamniquine, which occur less frequently than common nervous system effects, include nausea, vomiting, abdominal pain, anorexia and diarrhea.

Urticaria, rash, pruritus, and joint pain have been reported in some patients receiving oxamniquine. Fever, which occurs 1-5 days after administration of oxamniquine and persists for 2-5 days before defervescence, has been reported in patients receiving the drug for treatment of schistosomiasis principally in Egypt; fever reportedly has not occurred following im administration of the drug to healthy, uninfected adults. Minor, nonspecific ECG changes and pulmonary radiographic changes, principally characterized by pulmonary condensations have occurred in a few patients.

Minimal increases in eosinophil count appear to occur frequently following treatment with oxamniquine; however, eosinophilia is also associated with schistosomiasis and may also be a consequence of a host mediated immunologic response to antigen release during drug induced killing of the worms. Increased erythrocyte sedimentation rate, increased reticulocyte count, and increased or decreased leukocyte count also have been reported in a few patients receiving the drug.

For more Human Toxicity Excerpts (Complete) data for OXAMNIQUINE (6 total), please visit the HSDB record page.

Although evidence of hepatic abnormalities has occurred in animals receiving relatively low doses of oxamniquine, no evidence of serious adverse hepatic effects has developed in humans, even in patients with schistosomal infection associated with severe hepatosplenic involvement. Mild to moderate, transient increases in serum alkaline phosphatase, AST (SGOT) and/or ALT (SGPT) concentrations have occurred in patients receiving the drug; however, these abnormalities generally were not considered drug related and were not clinically important.

Oxamniquine has generally been reported to lack mutagenic activity as determined by various assay methods including cytogenetic, dominant lethal, and host mediated assays; however, as high concentrations, evidence of weak mutagenic activity has been reported as determined by the Ames mutagenic assay with or without metabolic activation.

Oxamniquine has been shown to have embryocidal effects in mice and rabbits when given at dosages 10 times the usual human dosage.

LD50 Mouse im > 2000 mg/kg

LD50 Mouse oral 1300 mg/kg

LD50 Rabbit im > 1000 mg/kg

LD50 Rabbit oral 800 mg/kg

Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C. 321-392).

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed drug products, incl oxamniquine, approved on the basis of safety and effectiveness by FDA under sections 505 and 507 of the Federal Food, Drug, and Cosmetic Act. /From the Prescription Drug Product List/

P - Antiparasitic products, insecticides and repellents

QP - Antiparasitic products, insecticides and repellents

P02BA02

Oxamniquine is an anthelmintic with schistosomicidal activity against <i>Schistosoma mansoni</i>, but not against other Schistosoma spp. Oxamniquine causes worms to shift from the mesenteric veins to the liver where the male worms are retained; the female worms return to the mesentery, but can no longer release egg.

Oxamniquine may associate with an irreversible inhibition of the nucleic acid metabolism of the parasites. A hypothesis has been put forth that the drug is activated by a single step, in which a schistosome sulfotransferase enzyme converts oxamniquine into an ester (probably acetate, phosphate, or sulfate). Subsequently, the ester spontaneously dissociates, the resulting electrophilic reactant is capable of alkylation of schistosome DNA.

Causes the worms to be dislodged from their usual site of residence in the mesenteric veins to the liver where they are retained and subsequently killed by host tissue reactions (eg, phagocytosis). The dislodgment of worms appears to result principally from contraction and paralysis of their musculature and subsequent immobilization of their suckers, which causes the worms to detach from the blood vessel wall, thereby allowing passive dislodgement by normal blood flow.

Hycanthone-sensitive and hycanthone-resistant schistosomes (which are also sensitive and resistant to oxamniquine) were exposed in vitro to tritium-labelled oxamniquine. The initial uptake of the drug into the schistosomes was essentially the same for the 2 strains. The homogenate of worms incubated with tritiated oxamniquine was fractionated and a purified DNA fraction was obtained by ethanol precipitation, RNAase and protease digestion, repeated phenolchloroform extractions, cesium chloride gradient centrifugation and extensive dialysis. The DNA fraction from sensitive worms contained radioactive oxamniquine at a level corresponding to about 1 drug molecule per 50,000 base pairs, while the DNA from resistant worms contained essentially no drug. The results support the hypothesis that oxamniquine, like hycanthone, exerts its activity by alkylating macromolecules of sensitive schistosomes.

1-2.5 hours

Oxamniquine has a plasma half-life of about 1-2.5 hours.

Probably hepatic

The drug is extensively metabolized, principally in the GI mucosa and/or lumen via enzymatic oxidation of the 6-hydroxymethyl group to the 6-carboxylic acid metabolite. Trace amounts of the 2-carboxylic acid metabolite have also been observed in urine, which reflects oxidation of the side chain. These metabolites do not possess antichistosomal activity.

0O977R722D

OXAMNIQUINE

Established Pharmacologic Class [EPC] - Anthelmintic

Oxamniquine is an Anthelmintic.

Well absorbed orally

Oxamniquine and its metabolites are excreted mainly in urine. Approximately 40-75% of an oral dose of the drug is excreted in urine within 24 hours of administration, principally as the 6-carboxylic acid metabolite. About 0.5-2% of an oral dose is excreted in urine unchanged; less than 1% of a dose is excreted in urine as the 2-carboxylic acid metabolite.

Oxamniquine is well absorbed following oral administration. The rate and extent of GI absorption of the drug are decreased by the presence of food. Peak plasma concentrations of oxamniquine occur approximately 1-3 hours after oral administration of usual doses of the drug. ... Interpatient variation in plasma oxamniquine concentrations may result from biodegradation of the drug in the GI mucosa during absorption. ... Oxamniquine undergoes extensive first pass metabolism in the GI lumen before absorption and/or in the GI mucosa during absorption in animals.

Following oral administration of a single 15 mg/kg dose of oxamniquine in adults and children with Schistosoma mansoni infection in one study, peak serum drug concentrations of 70-2595 and 89-1500 ng/ml, respectively, occurred at 1.5-3 hours. In another study, following oral administration of a single 1 g dose of oxamniquine in patients with advaced hepatosplenic schistosomiasis and in healthy adults, mean peak plasma drug concentrations of 1267 ng/ml at about 1.7 hours and 1983 ng/ml at about 1.4 hours occurred, respectively.