Eflornithine, also known as difluoromethylornithine (DFMO), is an ornithine decarboxylase inhibitor that is indicated for oral use to reduce the risk of relapse in adult and pediatric patients with high-risk neuroblastoma who have demonstrated at least a partial response to prior multi-agent, multimodality therapy including anti-GD2 immunotherapy. Myelosuppression, hepatotoxicity, and hearing loss have been reported with oral eflornithine therapy. Although unavailable on the US market, eflornithine cream is used to reduce unwanted facial hair in women and IV eflornithine is used to treat African trypanosomiasis (sleeping sickness) and Pneumocystis pneumonia. Parenteral eflornithine is only available from the World Health Organization and the Centers for Disease Control and Prevention.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Oral Administration
Oral Solid Formulations
-Administer eflornithine tablets orally with or without food.
-Tablets may be swallowed whole, chewed, or crushed.
-If a dose is missed, administer the missed dose as soon as possible. If the next scheduled dose is due within 7 hours, then skip the missed dose and give the next dose at the regularly scheduled time.
-If vomiting occurs after taking a dose, do not administer an additional dose. Give the next dose at the regularly scheduled time.
Crushed Tablet Preparation:
-Mix crushed tablet(s) with 2 tablespoonfuls (30 mL) of soft food or liquid.
-Confirm the entire contents are consumed; if any crushed tablet particles remain, mix with an additional small volume (e.g., no more than 30 mL) of soft food or liquid.
-Discard crushed tablet preparation after 1 hour from mixing.
Injectable Administration
-For intravenous infusion only.
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
Intravenous Administration
-Eflornithine injection is hypertonic and must be diluted with sterile water for injection prior to IV infusion administration.
-Solutions within 10% of plasma tonicity can be prepared by using 1 part eflornithine injection to 4 parts sterile water for injection, by volume. For example, to prepare four 5000 mg doses (usual trypanosomiasis dose for 50 kg patient): withdraw 100 mL from the eflornithine 200 mg/mL vial, then inject 25 mL (5 g) into each of four 100 mL (sterile water) IV diluent bags. The resulting eflornithine concentration will be 40 mg/mL (5000 mg per 125 mL total volume) in each IV bag.
-After mixing, the injection solution can be stored at 4 degrees C (39 degrees F) for up to 24 hours.
-Administer each dose by IV infusion over a period of at least 45 minutes.
Topical Administration
Cream/Ointment/Lotion Formulations
Vaniqa cream
-Eflornithine cream is for external use only.
-Apply a thin layer of cream to the affected areas of the face and adjacent involved areas under the chin; rub in thoroughly.
-Do not wash the treatment areas for at least 4 hours after cream application.
-Wait a few minutes after eflornithine application to apply cosmetics or sunscreen.
-If you miss a dose, skip the dose and apply the next dose at the regularly scheduled time.
Extremity pain occurred in less than 5% of pediatric subjects (median age, 4 years; range, 1 to 17 years) with high-risk neuroblastoma who received oral eflornithine as maintenance therapy in a clinical trial (n = 85).
Rash and alopecia were each reported in less than 5% of pediatric subjects (median age, 4 years; range, 1 to 17 years) with high-risk neuroblastoma who received oral eflornithine as maintenance therapy in a clinical trial (n = 85). Alopecia (3% to 10%) and pruritus have been reported with IV eflornithine. Acne vulgaris (10.8%), pseudo-folliculitis barbae (4.9%), stinging skin (4.1%), burning skin (3.5%), xerosis (3.3%), pruritus (3.1%), erythema (2.5%), tingling skin (2.2%), skin irritation (1.8%), rash (1.5%), alopecia (1.3%), folliculitis (1%), ingrown hair (0.9%), and facial edema (0.7%) were reported in subjects who received eflornithine cream for the reduction of unwanted facial hair in vehicle-controlled and open-label safety studies. Other dermatological adverse events that occurred in less than 1% of subjects include bleeding skin, cheilitis, contact dermatitis, swelling of lips, herpes simplex, numbness, and rosacea.
Severe neutropenia (grade 3 or 4, 4.2%), anemia (grade 3, 3.3%), and thrombocytopenia (grade 3 or 4, 1.4%) occurred in subjects younger than 21 years with high-risk neuroblastoma who received oral eflornithine as maintenance therapy in a pooled safety analysis (n = 360). Additionally, bone marrow failure was reported in 1 subject. Therapy interruption, a dosage reduction, or discontinuation may be necessary in persons who develop severe myelosuppression. Decreased neutrophil count (9%; grade 3 or 4, 8%), decreased hemoglobin concentration (4.7%; grade 3, 2.4%), decreased white blood cell count/leukopenia (2.4%), and decreased platelet count (1.2%) occurred in pediatric subjects (median age, 4 years; range, 1 to 17 years) with high-risk neuroblastoma who received oral eflornithine as maintenance therapy in a clinical trial (n = 85). Hematologic adverse events, including anemia (40% to 55%), leukopenia (20% to 37%), and thrombocytopenia (14% to 50%), have been reported with IV eflornithine.
Headache (4%), dizziness (1.3%), and vertigo (0.1%) were reported in subjects who received eflornithine cream for the reduction of unwanted facial hair in vehicle-controlled and open-label safety studies (n = 1,373). Seizures (4% to 10%) have been reported with IV eflornithine use and are generally isolated or respond to treatment; seizures are associated with higher CSF concentrations and occur more commonly in cases of relapse (12%) compared to new cases (4%). Tremor, headache, and dizziness have also been reported with IV eflornithine.
Diarrhea occurred in 5% of subjects younger than 21 years with high-risk neuroblastoma who received oral eflornithine as maintenance therapy in a pooled safety analysis (n = 360). Diarrhea including colitis (15%; grade 3, 3.5%) and vomiting (11%; grade 3, 1.2%) were reported in pediatric subjects (median age, 4 years; range, 1 to 17 years) with high-risk neuroblastoma who received oral eflornithine as maintenance therapy in a clinical trial (n = 85). Begin supportive treatment (e.g., anti-emetic or antidiarrheal medications) in persons who develop grade 3 nausea, vomiting, or diarrhea. Continue eflornithine at the current dosage if symptoms respond to supportive treatment. If symptoms do not respond to supportive treatment, hold eflornithine until the toxicity resolves to grade 2 or less and then resume eflornithine therapy at a reduced dosage. Gastrointestinal adverse events (5% to 38%) associated with IV eflornithine include abdominal pain, diarrhea, nausea, vomiting. Dyspepsia (1.9%), anorexia (0.7%), and nausea (0.7%) were reported in subjects who received eflornithine cream for the reduction of unwanted facial hair in vehicle-controlled and open-label safety studies.
Hearing loss and tinnitus have been reported with the use of eflornithine. New or worsening hearing loss (13%), hearing loss requiring new use of hearing aids (7%), and hearing loss worsened from baseline to grade 3 or 4 (12%) occurred in subjects younger than 21 years with high-risk neuroblastoma who received oral eflornithine as maintenance therapy in a pooled safety analysis (n = 360). Additionally, tinnitus was reported in 1 subject. Therapy interruption, a dosage reduction, or discontinuation may be necessary in persons who develop new or worsening hearing loss. Grade 3 hearing loss occurred in 7% of pediatric subjects (median age, 4 years; range, 1 to 17 years) with high-risk neuroblastoma who received oral eflornithine as maintenance therapy in a clinical trial (n = 85). Ototoxicity has been reported in up to 20% of subjects receiving IV eflornithine.
Infection including ear infection/otitis media (10%) and pneumonia (5%) occurred in subjects younger than 21 years with high-risk neuroblastoma who received oral eflornithine as maintenance therapy in a pooled safety analysis (n = 360). Additionally, otitis media (32%; grade 3, 2.4%), sinusitis (13%), pneumonia (12%; grade 3, 1.2%), upper respiratory tract infection (11%), conjunctivitis (11%), skin infection (7%; grade 3, 4.7%), and urinary tract infection (6%; grade 3, 1.2%) occurred in pediatric subjects (median age, 4 years; range, 1 to 17 years) with high-risk neuroblastoma who received oral eflornithine as maintenance therapy in a clinical trial (n = 85). Deep tissue infection has been reported with IV eflornithine.
Cough (15%) and allergic rhinitis (11%) occurred in pediatric subjects (median age, 4 years; range, 1 to 17 years) with high-risk neuroblastoma who received oral eflornithine as maintenance therapy in a clinical trial (n = 85).
Fever occurred in 7% of subjects younger than 21 years with high-risk neuroblastoma who received oral eflornithine as maintenance therapy in a pooled safety analysis (n = 360). Additionally, fever occurred in 11% (grade 3, 1.2%) of pediatric subjects (median age, 4 years; range, 1 to 17 years) with high-risk neuroblastoma who received oral eflornithine as maintenance therapy in a clinical trial (n = 85). Fever has been reported with IV eflornithine.
Elevated hepatic enzymes including grade 3 or 4 increased ALT (11%) and AST (6%) concentrations occurred in subjects younger than 21 years with high-risk neuroblastoma who received oral eflornithine as maintenance therapy in a pooled safety analysis (n = 360). Perform more frequent liver function testing monitoring in persons who develop transaminase or bilirubin concentration elevations. Therapy interruption, a dosage reduction, or discontinuation may be necessary in persons who develop severe hepatotoxicity. Additionally, increased ALT (9%; grade 3, 7%), AST (8%; grade 3, 6%), and alkaline phosphatase (4.7%; grade 3, 2.4%) concentrations were reported in pediatric subjects (median age, 4 years; range, 1 to 17 years) with high-risk neuroblastoma who received oral eflornithine as maintenance therapy in a clinical trial (n = 85).
Decreased potassium concentration/hypokalemia (grade 3, 2.4%), decreased sodium concentration/hyponatremia (grade 3, 2.4%), and increased potassium concentration/hyperkalemia (1.2%) occurred in pediatric subjects (median age, 4 years; range, 1 to 17 years) with high-risk neuroblastoma who received oral eflornithine as maintenance therapy in a clinical trial (n = 85).
Decreased glucose concentration/hypoglycemia (2.4%; grade 3 or 4, 1.1%) and increased glucose concentration/hyperglycemia (1.2%) occurred in pediatric subjects (median age, 4 years; range, 1 to 17 years) with high-risk neuroblastoma who received oral eflornithine as maintenance therapy in a clinical trial (n = 85).
Asthenia was reported in 0.3% of subjects who received eflornithine cream for the reduction of unwanted facial hair in vehicle-controlled and open-label safety studies.
Monitor complete blood counts prior to starting and periodically during treatment with eflornithine. Therapy interruption, a dosage reduction, or discontinuation may be necessary in patients who develop severe myelosuppression (e.g., anemia, neutropenia, thrombocytopenia).
Monitor liver function tests (LFTs) (e.g., ALT, AST, and total bilirubin levels) prior to starting eflornithine, every month for the first 6 months of treatment, and then once every 3 months or as clinically indicated during eflornithine therapy. Perform more frequent LFT monitoring in patients who develop hepatic disease/impairment (i.e., transaminase or bilirubin level elevations). Therapy interruption, a dosage reduction, or discontinuation may be necessary in patients who develop severe hepatotoxicity.
Monitor patients who receive eflornithine for hearing impairment/loss. Perform audiogram testing prior to starting eflornithine and at 6 -month intervals or as clinically indicated during eflornithine therapy. Therapy interruption, a dosage reduction, or discontinuation may be necessary in patients who develop new or worsening hearing loss.
Based on findings from animal studies and its mechanism of action, eflornithine may cause fetal harm when administered during pregnancy. Advise patients who are pregnant or who may become pregnant of the potential risk to a fetus. Although there are no available data on the use of eflornithine in pregnant patients, oral administration of eflornithine to pregnant rats and rabbits during organogenesis resulted in post-implantation loss, reduced fetal body weights, and an increased incidence of skeletal variations at doses equivalent to the recommended human dose. Both topical and intravenous eflornithine are classified as FDA pregnancy risk category C. Topical eflornithine, in studies that prevented animal ingestion from application sites, has not been associated with maternal or fetal teratogenic effects at doses up to 29 times the maximum recommended human dose. In clinical trials, 19 pregnancies occurred in women using topical eflornithine, resulting in 9 healthy infants, 4 spontaneous abortions, 5 elective abortions, and 1 Down's syndrome infant. The manufacturer of topical eflornithine recommends weighing the risk/benefit ratio with serious consideration of avoiding eflornithine therapy during pregnancy.
Counsel patients about the reproductive risk and contraception requirements during eflornithine treatment. Pregnancy testing should be performed prior to starting eflornithine in patients of reproductive potential. These patients should use effective contraception during and for 1 week after the last eflornithine dose. Due to the risk of male-mediated teratogenicity, patients should use effective contraception to avoid potential drug exposure in partners of reproductive potential during therapy and for 1 week after the last eflornithine dose.
It is not known if eflornithine is secreted in human milk or if it has effects on the breastfed child or on milk production. Because of the potential for serious adverse reactions in a breastfed child, advise patients against breast-feeding during eflornithine therapy and for 1 week after the last dose. It is not known if topical eflornithine is excreted into human milk and caution should be exercised if eflornithine is administered during breast-feeding. However, less than 1% of topical eflornithine is absorbed through the skin.
Per the manufacturer, this drug has been shown to be active against most strains of the following microorganisms either in vitro and/or in clinical infections: Trypanosoma brucei gambiense
NOTE: The safety and effectiveness in treating clinical infections due to organisms with in vitro data only have not been established in adequate and well-controlled clinical trials.
For the reduction of unwanted facial hair, including hirsutism of the face:
NOTE: Eflornithine cream has been studied on the face and adjacent involved areas under the chin of affected individuals. Therefore, limit use to these areas of involvement.
Topical Dosage:
Adult and Adolescent females: Apply a thin layer twice daily, at least 8 hours apart, to affected facial area(s). Rub the cream into the skin thoroughly. Do not wash the treated area for at least 4 hours. Other hair removal methods may be used in conjunction with eflornithine cream; apply at least 5 minutes after hair removal. Improvement may occur as early as 4 to 8 weeks after starting treatment; however, improvement may take longer in some patients. Discontinue use if no improvement is seen after 6 months of use. Using the Physician's Global Assessment (PGA), 32% of female patients who received up to 24 weeks of twice-daily eflornithine cream (n = 393) had a marked improvement or greater in unwanted facial hair reduction compared with 8% of female patients who received vehicle only (n = 201) in a pooled analysis of 2 randomized, double-blind studies.
For the treatment of second-stage (meningoencephalitic) African trypanosomiasis (sleeping sickness) due to T. brucei gambiense:
NOTE: Eflornithine has been designated an orphan drug by the FDA for the treatment of African trypanosomiasis (sleeping sickness).
NOTE: For treatment advice and to obtain eflornithine, health care providers should contact the Centers for Disease Control and Prevention Division of Parasitic Diseases and Malaria.
-for the treatment of second-stage (meningoencephalitic) African trypanosomiasis due to T. brucei gambiense in combination with nifurtimox (NECT):
Intravenous dosage:
Adults: 200 mg/kg/dose IV every 12 hours for 7 days in combination with nifurtimox for 10 days.
Infants, Children, and Adolescents: 200 mg/kg/dose IV every 12 hours for 7 days in combination with nifurtimox for 10 days.
-for the treatment of second-stage (meningoencephalitic) African trypanosomiasis due to T. brucei gambiense as monotherapy:
Intravenous dosage:
Adults: 100 mg/kg/dose IV every 6 hours for 14 days when combination therapy with nifurtimox or monotherapy with fexinidazole is not possible. An active immune system is required to achieve a cure.
Children and Adolescents 12 to 17 years: 100 mg/kg/dose IV every 6 hours for 14 days when combination therapy with nifurtimox or therapy with fexinidazole is not possible. An active immune system is required to achieve a cure.
Infants and Children 1 month to 11 years: 100 to 150 mg/kg/dose IV every 6 hours for 14 days when combination therapy with nifurtimox or therapy with fexinidazole is not possible. An active immune system is required to achieve a cure.
For the treatment of neuroblastoma:
NOTE: Eflornithine is designated as an orphan drug by the FDA for this indication.
-for the treatment of high-risk neuroblastoma to reduce the risk of relapse in patients who have had at least a partial response to prior multi-agent, multimodality therapy, including anti-GD2 immunotherapy:
Oral dosage:
Adults: Dose is based on body surface area (BSA) as follows: 768 mg orally twice daily for BSA of more than 1.5 m2 and 576 mg orally twice daily for BSA of 0.75 m2 to 1.5 m2. Continue treatment until disease progression or for a maximum of 2 years. Recalculate the BSA dosage every 3 months during treatment. Therapy interruption, a dosage reduction, or discontinuation may be necessary in patients who develop severe toxicity. In a prospectively designed, externally controlled analysis, event-free survival (hazard ratio (HR) = 0.48; 95% CI, 0.27 to 0.85), the protocol-specified primary analysis, and overall survival (HR = 0.32; 95% CI, 0.15 to 0.7) were significantly improved in propensity-score matched patients (median age, 3 years; range, 0.1 to 20.1 years) with high-risk neuroblastoma who received eflornithine (n = 90; from a phase 2 [NMTRC003B/003b] trial) compared with dinutuximab, granulocyte-macrophage colony-stimulating factor, interleukin-2, and cis-retinoic acid (n = 270; from a phase 3 [ANBL0032] trial) as maintenance therapy after achieving at least a partial response to prior induction and consolidation therapy. In this analysis, 86% of patients had stage 4 disease and 44% of patients had MYCN-amplified tumors.
Infants, Children, and Adolescents: Dose is based on body surface area (BSA) as follows: 192 mg orally twice daily for a BSA of 0.25 m2 to less than 0.5 m2; 384 mg orally twice daily for a BSA of 0.5 m2 to less than 0.75 m2; 576 mg orally twice daily for a BSA of 0.75 m2 to 1.5 m2; and 768 mg orally twice daily for a BSA of more than 1.5 m2. Continue treatment until disease progression or for a maximum of 2 years. Recalculate the BSA dosage every 3 months during treatment. Therapy interruption, a dosage reduction, or discontinuation may be necessary in patients who develop severe toxicity. In a prospectively designed, externally controlled analysis, event-free survival (hazard ratio (HR) = 0.48; 95% CI, 0.27 to 0.85), the protocol-specified primary analysis, and overall survival (HR = 0.32; 95% CI, 0.15 to 0.7) were significantly improved in propensity-score matched patients (median age, 3 years; range, 0.1 to 20.1 years) with high-risk neuroblastoma who received eflornithine (n = 90; from a phase 2 [NMTRC003B/003b] trial) compared with dinutuximab, granulocyte-macrophage colony-stimulating factor, interleukin-2, and cis-retinoic acid (n = 270; from a phase 3 [ANBL0032] trial) as maintenance therapy after achieving at least a partial response to prior induction and consolidation therapy. In this analysis, 86% of patients had stage 4 disease and 44% of patients had MYCN-amplified tumors.
Therapeutic Drug Monitoring:
Management of Treatment-Related Toxicity
Recommended Oral Tablet Dosage Reductions
NOTE: If subsequent adverse reactions occur, continue dose reduction until reaching the minimum dose.
768 mg twice daily: reduce to 576 mg twice daily;
576 mg twice daily: reduce to 384 mg twice daily;
384 mg twice daily: reduce to 192 mg twice daily;
192 mg twice daily: reduce to 192 mg once daily.*
* Permanently discontinue therapy if 192 mg once daily is not tolerated.
Hearing Loss
Clinically concerning new or worsening hearing loss compared to baseline audiogram: Continue eflornithine therapy at current dosage and repeat an audiogram in 3 weeks. Resume eflornithine at the same dosage if audiogram results are improved. If clinically concerning changes persist, hold eflornithine therapy for up to 30 days and repeat audiogram. If audiogram results are stable or improved, resume eflornithine at a reduced dosage.
Hematologic Toxicity
Anemia (hemoglobin concentration (Hgb) less than 8 g/dL): Hold eflornithine therapy until Hgb is 8 g/mL or more; resume therapy at the same dosage. If anemia recurs, hold eflornithine until Hgb is 8 g/mL or more and then resume therapy at a reduced dosage.
Neutropenia (absolute neutrophil count (ANC) less than 500 cells/mm3): Hold eflornithine therapy until ANC is 500 cells/mm3 or more. Resume eflornithine at the same dosage if counts recover within 7 days; resume eflornithine at a reduced dosage if counts recover after 7 days.
Thrombocytopenia (platelet count of less than 25,000 cells/mm3): Hold eflornithine therapy until platelet count is 25,000 cells/mm3 or more. Resume eflornithine at the same dosage if counts recover within 7 days; resume eflornithine at a reduced dosage if counts recover between 7 and 14 days. Permanently discontinue therapy if platelet counts do not recover within 14 days.
Hepatotoxicity
Elevated AST or ALT levels by 10 times the ULN or more: Hold eflornithine therapy until transaminase levels are less than 10 times the ULN. Resume eflornithine at the same dosage if counts recover within 7 days; resume eflornithine at a reduced dosage if counts recover after 7 days.
Nausea, Vomiting, or Diarrhea
Grade 3 toxicity: Begin supportive treatment, such as anti-emetic or antidiarrheal medication. Continue eflornithine at the current dosage if symptoms respond to supportive treatment. If symptoms do not respond to supportive treatment, hold eflornithine until the toxicity resolves to grade 2 or less and then resume eflornithine therapy at a reduced dosage.
Other Severe Adverse Reactions
Grade 3 or 4 toxicity: Hold eflornithine until the toxicity resolves to grade 2 or less and then resume eflornithine therapy at a reduced dosage.
Recurrent Grade 4 toxicity: Permanently discontinue therapy.
Maximum Dosage Limits:
-Adults
400 mg/kg per day IV.
BSA more than 1.5 m2: 1,536 mg/day PO.
BSA of 0.75 m2 to 1.5 m2: 1,152 mg/day PO.
-Geriatric
400 mg/kg per day IV.
BSA more than 1.5 m2: 1,536 mg/day PO.
BSA of 0.75 m2 to 1.5 m2: 1,152 mg/day PO.
-Adolescents
500 mg/kg per day IV.
BSA more than 1.5 m2: 1,536 mg/day PO.
BSA of 0.75 m2 to 1.5 m2: 1,152 mg/day PO.
-Children
500 mg/kg per day IV.
BSA more than 1.5 m2: 1,536 mg/day PO.
BSA of 0.75 m2 to 1.5 m2: 1,152 mg/day PO.
BSA of 0.5 m2 to less than 0.75 m2: 768 mg/day P
BSA of 0.25 m2 to less than 0.5 m2: 384 mg/day PO.
-Infants
384 mg/day PO.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Patients with Renal Impairment Dosing
Specific guidelines for oral dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
A reduced initial dosage may be necessary with IV administration; adjust gradually according to clinical response and tolerance.
*non-FDA-approved indication
There are no drug interactions associated with Eflornithine products.
Eflornithine is an irreversible inhibitor of the ornithine decarboxylase (ODC), a rate-limiting enzyme in the biosynthesis of polyamines and a transcriptional target of the MYCN gene. Polyamines are involved in differentiation and proliferation of mammalian cells and may play a role in neoplastic transformation. Inhibition of polyamine synthesis may restore the balance of the LIN28/Let-7 metabolic pathway resulting in decreased expression of the oncogenic drivers MYCN and LIN28B in MYCN-amplified neuroblastoma. Eflornithine prevented or delayed tumor formation with limiting dilutions of MYCN-amplified neuroblastoma cells in mice. It exhibited a cytostatic effect in MYCN-amplified and MYCN non-amplified neuroblastoma cells in vitro.
In sleeping sickness, eflornithine deprives the trypanosomes of ODC and polyamine synthesis for a prolonged period compared with mammalian cells, leading to cessation of replication and growth of the parasite. Eflornithine exerts trypanostatic action. Eflornithine is not considered universally effective against the Trypanosoma class of organisms; the drug does not appear to adequately treat sleeping sickness caused by Trypanosoma rhodesiense. Similarly, ODC activity has been detected in Pneumocystis and accounts for eflornithine activity in PCP.
Topical eflornithine may irreversibly inhibit skin ODC activity and affect the rate of hair growth in hair follicles. ODC activity correlated with DNA replicative activity in basal cells and in hair matrix cells of mouse epidermis.
Eflornithine is administered orally, intravenously, and topically. It does not bind to human plasma proteins. Eflornithine has a volume of distribution of 24.3 L, a terminal plasma elimination half-life of 3.5 hours, and clearance of 5.3 L/hour.
-Route-Specific Pharmacokinetics
Oral Route
Following oral administration, peak plasma levels of eflornithine were achieved at 3.5 hours post dose.
Effects of Food: The Cmax and AUC values of eflornithine were not affected by food containing high fat and high calories. Additionally, crushing tablets in a standard pudding admixture had no effect on eflornithine exposure.
Intravenous Route
Eflornithine crosses the blood-brain barrier and produces cerebrospinal fluid to blood ratios between 0.13 and 0.51. One study suggests that CSF levels need to remain above 50 nmol/mL for a trypanosomiasis cure, but the amount of time concentrations need to remain above this level is unknown.
Topical Route
Following single or multiple topical eflornithine 13.9% cream applications, the mean percutaneous absorption was less than 1%; the apparent steady-state plasma half-life of eflornithine was approximately 8 hours. Steady state levels were reached within 4 days of twice daily application. The steady-state Cmax, Cmin, and AUC(0 to12 hr) values were approximately 10 nanograms (ng)/mL, 5 ng/mL, and 92 ng x hour/mL, respectively, after twice-daily application of 0.5 g of cream (total dose 1 g/day; 139 mg as anhydrous eflornithine hydrochloride) in patients with unwanted facial hair. Following topical application, the dose-normalized Cmax and AUC values were estimated to be decreased by approximately 100-fold and 60-fold, respectively, compared with oral eflornithine 370 mg given once daily.
-Special Populations
Hepatic Impairment
Mild hepatic impairment (bilirubin level at the ULN or less and AST level more than the ULN OR bilirubin level more than 1 times the ULN and any AST level) has no significant impact on eflornithine exposure.
Pediatrics
Age (range, 1 to 19 years) has no significant impact on eflornithine exposure. Higher failure rates of eflornithine in children versus adults are attributed to different pharmacokinetics in children, resulting in lower CSF concentrations at similar weight-adjusted doses.
Gender Differences
Sex has no significant impact on eflornithine exposure.
Obesity
Body surface area (range, 0.4 to 2 m2) has no significant impact on eflornithine exposure.