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Eflornithine (Systemic)

Primary: AP109

Commonly used brand name(s): Ornidyl.

Other commonly used names are
DFMO and alpha-difluoromethylornithine.
Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).

Not commercially available in Canada.


Antiprotozoal (systemic)—



Trypanosomiasis, African (treatment)—Eflornithine is indicated in the treatment of the meningoencephalitic stage of Trypanosoma brucei gambiense infection (West African sleeping sickness). {01} {02} {04} {08} {09} {10}

—Not all species or strains of a particular organism may be susceptible to eflornithine.


Physicochemical characteristics:
Molecular weight—
    236.65 {01}

Mechanism of action/Effect:

Eflornithine is an enzyme-activated, irreversible inhibitor of ornithine decarboxylase (ODC), the key enzyme in the conversion of ornithine to polyamines. Polyamines (putrescine, spermidine, and spermine) play an essential role in the growth, differentiation, and replication of cells by participating in nucleic acid and protein synthesis in protozoa, as well as in normal tissue and tumors in humans. Eflornithine's inhibition of ODC results in complete intracellular elimination of putrescine and a 60–75% reduction in spermidine, producing morphologic changes of trypanosomes in the bloodstream. {01} {02} {03} {04} {05} {06} Because the clearance of parasites from the bloodstream is slow, it is likely that eflornithine is cytostatic rather than cytolytic; in addition, animal studies have suggested that an intact immune response is probably necessary for complete elimination of the parasites from the bloodstream. {03} {04}


Well absorbed after oral administration; bioavailability approximately 50%. {04} {07}


Crosses the blood-brain barrier, with cerebrospinal fluid (CSF) concentrations reaching 6 to 51% of corresponding blood concentrations. One very small study found higher penetration into the CSF of patients with the most severe form of the disease, suggesting that penetration into the CSF may be related to the degree of CNS involvement. {02} {04}

Vol D=0.30 to 0.43 L per kg. {05} {07}

Protein binding:

No significant plasma protein binding. {01}


Normal renal function—Elimination: 3.2 to 3.6 hours. {05} {07}

Time to peak serum concentration:

End of infusion. {07}

Mean peak serum concentration

196.6 to 317.9 mcg per mL after 100 mg per kg of body weight every 6 hours. {05}

    Renal; approximately 80% excreted unchanged in the urine within 24 hours. {01} {05} {07} The renal clearance of eflornithine approximates that of creatinine clearance. {01}

Precautions to Consider


Long-term studies in animals have not been performed to evaluate the carcinogenic potential of eflornithine. {01}


Eflornithine did not induce mutagenic changes in in vitro studies using Salmonella and 2 strains of Saccharomyces . {01}

Decreased spermatogenic effects and impaired fertility were found in rats and rabbits at doses equivalent to one-half the recommended human dose and in mice at approximately 2 times the human dose. {01}

Adequate and well-controlled studies in humans have not been done. {01} Eflornithine should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus. The meningoencephalitic stage of African trypanosomiasis has such a high mortality rate if left untreated that treatment with eflornithine may justify the potential risk to the fetus. {14}

Eflornithine has been shown to be contragestational in rats, rabbits, and mice given doses of 0.5, 0.5, and 2 times the human dose, respectively. In postnatal studies, retarded development was reported in rat pups receiving doses slightly higher than the human dose. {01}

FDA Pregnancy Category C. {01}


It is not known whether eflornithine is distributed into breast milk. However, problems in humans have not been documented. {01}


No information is available on the relationship of age to the effects of eflornithine in pediatric patients. Safety and efficacy have not been established. {01}


No information is available on the relationship of age to the effects of eflornithine in geriatric patients.


The bone marrow–depressant effects of eflornithine may result in an increased incidence of microbial infection, delayed healing, and gingival bleeding.

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

Note: Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.

» Bone marrow depressants, other (See Appendix II )    (concurrent use with eflornithine may increase the bone marrow–depressant effects of these medications and radiation therapy)

Ototoxic medications, other (See Appendix II ){15}    (concurrent use of these medications with long-term eflornithine therapy may increase the potential for ototoxicity)

Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).

Risk-benefit should be considered when the following medical problems exist
Eighth-cranial-nerve impairment, pre-existing{15}    (hearing loss has occurred in patients receiving long-term therapy with eflornithine for treatment of cancer and Pneumocystis carinii pneumonia [conditions in which efficacy of eflornithine has not been clearly demonstrated]; {15} although treatment for African trypanosomiasis is relatively short, the risk of hearing loss may still exist)

» Hematologic abnormalities, pre-existing    (eflornithine may cause anemia, leukopenia, or thrombocytopenia, worsening any pre-existing hematologic abnormalities)

» Renal function impairment{01}    (because eflornithine is excreted primarily through the kidneys and its renal clearance approximates that of the creatinine clearance, the dose of eflornithine may need to be reduced in patients with renal function impairment)

Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):

Audiograms, serial{05}{13}    (may be required prior to, periodically during, and following treatment, especially in patients with pre-existing eighth-cranial-nerve impairment or patients receiving long-term therapy)

» Complete blood counts (CBCs) and
» Platelet counts{01}    (because eflornithine may cause anemia, leukopenia, and thrombocytopenia, a complete blood count and platelet count should be performed before treatment, 2 times a week during therapy, and then weekly, thereafter, until blood counts return to baseline)

Side/Adverse Effects

Note: Most side effects are transient and reversible by discontinuing the drug or decreasing the dose. {02} {03} {04} Hematologic abnormalities occur frequently, ranging from 10–55%. {01} {05} {06} These abnormalities are dose-related and usually reversible. Thrombocytopenia is thought to be due to a production defect rather than to peripheral destruction. {06} Seizures were seen in approximately 8% of patients, but may be related to the disease state rather than the drug. {01} {02} {10}
Reversible sensorineural hearing loss has occurred in 30–70% of patients receiving long-term therapy (more than 4–8 weeks of therapy or a total dose of >300 grams) {13}; high-frequency hearing is lost first, followed by middle- and low-frequency hearing. {05} {13} Because treatment for African trypanosomiasis is short-term, patients are unlikely to experience hearing loss.

The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence more frequent
Hematologic abnormalities, {01}{02}{03}{04}{05}{06}{08}{09}{10}{11}{12} specifically anemia (unusual tiredness or weakness), leucopenia (sore throat and fever), or thrombocytopenia (unusual bleeding or bruising)

Incidence rare
Ototoxicity{03}{04}{05}{11}{13} (sensorineural hearing loss)

Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
Gastrointestinal disturbances (diarrhea; nausea; abdominal pain; vomiting){01}{02}{03}{04}{05}{06}{09}{10}{11}{12}

Incidence rare
Alopecia (hair loss){05}{09}

Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Eflornithine (Systemic).

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before receiving this medication
»   Conditions affecting use, especially:

Pregnancy—Because the meningoencephalitic stage of African trypanosomiasis has such a high mortality rate if left untreated, treatment with eflornithine justifies the potential risk to the fetus

Dental—The neutropenic and thrombocytopenic effects of eflornithine may result in an increased incidence of microbial infection, delayed healing, and gingival bleeding
Other medications, especially other bone marrow depressants
Other medical problems, especially hematologic disturbances or renal function impairment

Proper use of this medication
» Importance of receiving medication for full course of therapy and on a regular schedule

» Proper dosing

Precautions after receiving this medication
Regular visits to physician to check progress

Caution if bone marrow depression occurs
» Checking with physician immediately if fever or chills occur or if you think you are getting an infection
» Checking with physician immediately if unusual bleeding or bruising; black, tarry stools; blood in urine or stools; or pinpoint red spots on skin occur
Caution in use of regular toothbrushes, dental floss, and toothpicks; physician, dentist, or nurse may suggest alternative methods for cleaning teeth and gums; checking with physician before having dental work done
Using caution to avoid accidental cuts with use of sharp objects such as a safety razor or fingernail or toenail cutters

Side/adverse effects
Signs of potential side effects, especially hematologic disturbances, ototoxicity, and seizures

General Dosing Information
Severe anemia, leukopenia or thrombocytopenia requires an interruption in therapy until there is evidence of bone marrow recovery. {01}

Because eflornithine's excretion through the kidneys is approximately the same as creatinine clearance, patients with renal function impairment may need an adjustment in dosage, based on their creatinine clearance. {01}

Parenteral Dosage Forms


Usual adult and adolescent dose
Trypanosomiasis, African (treatment)
Intravenous infusion, 100 mg per kg of body weight, infused over at least forty-five minutes, every six hours for fourteen days. {01} {02} {09}

Usual pediatric dose
Safety and efficacy have not been established.

Strength(s) usually available

20,000 mg in 100 mL (Rx) [Ornidyl]

Not commercially available.

Packaging and storage:
Store below 30 °C (86 °F), unless otherwise specified by manufacturer. Protect from freezing and light.

Preparation of dosage form:
Eflornithine hydrochloride concentrate for injection is hypertonic and must be diluted with sterile water for injection before infusion. To prepare initial dilution for intravenous infusion, withdraw the entire 100 mL from the vial and add 25 mL of eflornithine into each of 4 containers with 100 mL of sterile water for injection. This produces a concentration of 40 mg per mL (5000 mg in 125 mL). {01}

After dilution with sterile water for injection, eflornithine must be used within 24 hours. Bags containing diluted eflornithine should be stored at 4 °C (39 °F) to minimize the risk of microbial proliferation. {01}

Eflornithine hydrochloride for injection should not be administered intravenously with any other drugs. {01}

Revised: 06/26/1995

  1. Ornidyl package insert (Marion Merrell Dow), Rev 11/90, Rec 3/91, Rec 4/95.
  1. Doua F, Boa FY, Schechter PJ, et al. Treatment of human late stage gambiense trypanosomiasis with -difluoromethylornithine (eflornithine): efficacy and tolerance in 14 cases in Cote D'Ivoire. Am J Trop Med Hyg 1987; 37(3): 525-33.
  1. Van Bogaert I, Haemers A. Eflornithine. A new drug in the treatment of sleeping sickness. Pharm Weekbl [Sci] 1989; 11(3): 69-75.
  1. Taelman H, Schechter PJ, Marcelis L, et al. Difluoromethylornithine, an effective new treatment of Gambian trypanosomiasis. Am J Med 1987; 82: 607-14.
  1. Sahai J, Berry AJ. Eflornithine for the treatment of Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome: a preliminary review. Pharmacotherapy 1989; 9(1): 29-33.
  1. Abeloff MD, Slavik M, Luk GD, et al. Phase I trial and pharmacokinetic studies of -difluoromethylornithine—an inhibitor of polyamine biosynthesis. J Clin Oncol 2/1984; 2(2): 124-30.
  1. Haegele KD, Alken RG, Grove J, et al. Kinetics of -difluoromethylornithine: an irreversible inhibitor of ornithine decarboxylase. Clin Pharmacol Ther 1981; 30(2): 210-6.
  1. di Bari C, Pastore G, Roscigno G, et al. Late-stage African trypanosomiasis and eflornithine. Ann Intern Med 1986; 105(5): 803-4.
  1. Pepin J, Guern C, Milord F, Schechter PJ. Difluoromethylornithine for arseno-resistant Trypanosoma brucei gambiense sleeping sickness. Lancet 1987; 2: 1431-3.
  1. Van Nieuwenhove S, Schechter PJ, Declerq J, et al. Treatment of gambiense sleeping sickness in the Sudan with oral DFMO (DL--difluoromethylornithine), an inhibitor of ornithine decarboxylase; first field trial. Trans R Soc Trop Med Hyg 1985; 79: 692-8.
  1. Ajani JA, Ota DM, Grossie Jr VB, et al. Evaluation of continuous-infusion alpha-difluoromethylornithine therapy for colorectal carcinoma. Cancer Chemother Pharmacol 1990; 26: 223-6.
  1. Rolston KVI, Fainstein V, Bodey GP. Intestinal cryptosporidiosis treated with eflornithine: a prospective study among patients with AIDS. J Acquir Immune Defic Syndr 1989; 2(5): 426-30.
  1. Jansen C, Mattox DE, Miller KD, et al. An animal model of hearing loss from -difluoromethylornithine. Arch Otolaryngol Head Neck Surg 1989; 115: 1234-7.
  1. USP Parasitology Advisory Panel meeting, 10/21/91.
  1. Reviewers' consensus on Eflornithine (Systemic) monograph draft of 10/91.