オキサムニキン

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

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.