Neurotoxicity in animals due to arteether and artemether

Brewer, Thomas G.; Peggins, James O.; Grate, Stephen J.; Petras, J.M.; Levine, Barry; Weina, Peter J.; Swearengen, James R.; Heiffer, Melvin H.; Schuster, Brian G.

doi:10.1016/0035-9203(94)90469-3

Cited by 230 publications

(119 citation statements)

References 7 publications

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“…11 Neurotoxic eff ects caused by artemisinin derivatives in animals and hearing loss by artemether-lumefantrine in people have raised concerns. 9,28 In our study, no adverse event indicating a possible neurotoxic eff ect of this drug combination (based on specifi c neurological examinations) and no adverse events related to the auditory system were reported, thereby confi rming, in a large group of patients, previous fi ndings. 29,30 The chemical similarity between lume fantrine and halofantrine, which causes QTc prolongation, led to scrutiny of electrocardiographic fi ndings in our study, which is thus the largest study addressing this issue prospectively.…”

Section: Discussionsupporting

confidence: 79%

Efficacy and safety of artemether-lumefantrine dispersible tablets compared with crushed commercial tablets in African infants and children with uncomplicated malaria: a randomised, single-blind, multicentre trial

et al. 2008

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Section: Discussionsupporting

confidence: 79%

Efficacy and safety of artemether-lumefantrine dispersible tablets compared with crushed commercial tablets in African infants and children with uncomplicated malaria: a randomised, single-blind, multicentre trial

et al. 2008

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“…Artemisinin derivatives have proved safe in humans, but high doses produce neurotoxicity in several mammalian species. 15 Previous studies with this regimen of artesunate have shown that nausea (21%), vomiting (13%), diarrhea (8%), and rash (4%) may develop during the first two days after treatment, but subside without intervention. 16 Two patients also developed dizziness after receiving mefloquine.…”

Section: Discussionmentioning

confidence: 90%

Polyclonal anti-tumor necrosis factor-alpha Fab used as an ancillary treatment for severe malaria.

Looareesuwan

Sjostrom²,

Krudsood³

et al. 1999

The American Journal of Tropical Medicine and Hygiene

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Abstract. Single doses (250, 500, 1,000, or 2,000 units/kg) of an ovine polyclonal-specific Fab fragment directed against tumor necrosis factor-␣ (TNF-␣) were given to 17 adult patients with severe falciparum malaria immediately before treatment with artesunate in a pilot study to assess safety and optimal dosage with a view to future studies. Clinical and laboratory variables were compared with 11 controls. In the groups given Fab, there was a tendency for a faster resolution of clinical manifestations and reduction of fever but also a tendency towards longer parasite clearance times. Adverse events were more common in the control group and no early anaphylactic or late serum sickness reactions occurred in the Fab treated patients. On admission all patients had markedly elevated levels of TNF-␣ (85-1,532 ng/L) and interleukin-6 (IL-6) (30-27,500 ng/L). Also, 86% had elevated interferon-␥ (IFN-␥) levels, 75% had increased IL-2 levels, 36% had increased IL-8 levels, and 21% had increased IL-1␤ levels. Antibody treatment reduced IFN-␥ concentrations in a dose-related manner, but had no obvious effects on levels of other cytokines in this small study, although unbound TNF-␣ was undetectable after Fab treatment. Circulating concentrations of soluble E-selectin, intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 were not affected by Fab treatment. The Fab exhibited a two-compartment, dose-proportional kinetics with an average elimination halflife of 12.0 hr, with about 20% being excreted renally. These results encourage a randomized, placebo-controlled trial in patients with cerebral malaria and provide some guidance about dosage.

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“…21 Two patterns of damage have been observed: irreversible neuronal loss leading to permanent neurologic deficit or death, and transient neurologic abnormalities with full recovery of function. The brain stem nuclei most affected include those involved in the auditory and vestibular relays.…”

Section: Discussionmentioning

confidence: 99%

“…Neurotoxicity in experimental animals has been associated particularly with the use of intramuscular injections of artemether or arteether. 21 These two oil-based compounds, which are released relatively slowly from the intramuscular injection site, are more toxic than the rapidly absorbed water-soluble artesunate. 22 Intramuscular administration of artemether or arteether is also more neurotoxic than oral administration of the same drugs.…”

Section: Discussionmentioning

confidence: 99%

Adverse effects in patients with acute falciparum malaria treated with artemisinin derivatives.

Price

Vugt²,

Phaipun³

et al. 1999

Am J Trop Med Hyg

235

124

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Abstract. In prospective studies of acute uncomplicated, multidrug-resistant falciparum malaria on the western border of Thailand, the oral artemisinin derivatives were used alone in the treatment of 836 patients (artesunate 630, artemether 206), were combined with mefloquine (15-25 mg base/kg) in 2,826 patients, and mefloquine alone was used in 1,303 patients. The combined regimens of mefloquine plus an artemisinin derivative were associated with more side effects than those with an artemisinin derivative alone; acute nausea (31% versus 16%), vomiting (24% versus 11%), anorexia (51% versus 34%), and dizziness (47% versus 15%) (P Ͻ 0.001). Oral artesunate and artemether alone were very well tolerated. There was no difference in the incidence of possible adverse effects between the two drugs, and no evidence that either derivative caused allergic reactions, neurologic or psychiatric reactions, or cardiovascular or dermatologic toxicity. Blackwater fever occurred in three patients treated with mefloquine plus artesunate regimens. Oral artesunate and artemether are safe and well tolerated antimalarial drugs.

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Neurotoxicity in animals due to arteether and artemether

Cited by 230 publications

References 7 publications

Efficacy and safety of artemether-lumefantrine dispersible tablets compared with crushed commercial tablets in African infants and children with uncomplicated malaria: a randomised, single-blind, multicentre trial

Efficacy and safety of artemether-lumefantrine dispersible tablets compared with crushed commercial tablets in African infants and children with uncomplicated malaria: a randomised, single-blind, multicentre trial

Polyclonal anti-tumor necrosis factor-alpha Fab used as an ancillary treatment for severe malaria.

Adverse effects in patients with acute falciparum malaria treated with artemisinin derivatives.

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