No

Antiprotozoal

Treatment of meningoencephalitic stage of Trypanosoma brucei gambiense infection (sleeping sickness)

C

Hypersensitivity to eflornithine or any component

Must be diluted before use; frequent monitoring for myelosuppression should be done; use with caution in patients with a history of seizures and in patients with renal impairment; serial audiograms should be obtained; due to the potential for relapse, patients should be followed up for at least 24 months

>10%: Hematologic (reversible): Anemia (55%), leukopenia (37%), thrombocytopenia (14%)

1% to 10%:

Central nervous system: Seizures (may be due to the disease) (8%), dizziness

Dermatologic: Alopecia

Gastrointestinal: Vomiting, diarrhea

Hematologic: Eosinophilia

Otic: Hearing impairment

<1%: Facial edema, headache, abdominal pain, anorexia, weakness

No known antidote; treatment is supportive; in mice and rats, CNS depression, seizures, death have occurred

Must be diluted before use and used within 24 hours of preparation

Eflornithine exerts antitumor and antiprotozoal effects through specific, irreversible ("suicide") inhibition of the enzyme ornithine decarboxylase (ODC). ODC is the rate-limiting enzyme in the biosynthesis of putrescine, spermine, and spermidine, the major polyamines in nucleated cells. Polyamines are necessary for the synthesis of DNA, RNA, and proteins and are, therefore, necessary for cell growth and differentiation. Although many microorganisms and higher plants are able to produce polyamines from alternate biochemical pathways, all mammalian cells depend on ornithine decarboxylase to produce polyamines. Eflornithine inhibits ODC and rapidly depletes animal cells of putrescine and spermidine; the concentration of spermine remains the same or may even increase. Rapidly dividing cells appear to most susceptible to the effects of eflornithine.

Absorption: Well absorbed from GI tract

Bioavailability: 54% to 58%

Half-life: 3-3.5 hours

Elimination: Mainly excreted unchanged in urine via glomerular filtration

Adults: I.V. infusion: 100 mg/kg/dose given every 6 hours (over at least 45 minutes) for 14 days

CBC with platelet counts

Dizziness is common

Leukopenia is common; use caution with clozapine and carbamazepine

No information available to require special precautions

No effects or complications reported

Report any persistent or unusual fever, sore throat, fatigue, bleeding, or bruising; frequent blood tests are needed during therapy

Injection, as hydrochloride: 200 mg/mL (100 mL)

Barbarash RA, Toll L, and Sahn SA, "Alpha-Difluoromethylornithine Infusion and Cardiac Arrest," Ann Intern Med, 1986, 105(1):141-2.

"Drugs for Parasitic Infections," Med Lett Drugs Ther, 1993, 35(911):111-22.

Haegele KD, Alken RG, Grove J, et al, "Kinetics of a-Difluoromethylornithine: An Irreversible Inhibitor of Ornithine Decarboxylase," Clin Pharmacol Ther, 1981, 30(2):210-7.