Version July 2025
Neuroblastoma, high risk (Iwilfin only): Note: Recalculate the BSA dose every 3 months during treatment.
Oral:
|
BSA |
Eflornithine oral dosage |
|---|---|
|
>1.5 m2 |
768 mg twice daily; continue until disease recurrence, unacceptable toxicity, or a maximum of 2 years. |
|
0.75 m2 to 1.5 m2 |
576 mg twice daily; continue until disease recurrence, unacceptable toxicity, or a maximum of 2 years. |
Missed doses: Oral: Administer the missed dose as soon as possible; if the next dose is due within 7 hours, the missed dose should be skipped. If vomiting occurs following administration, do not administer an additional dose; continue dosing with next scheduled dose.
West African trypanosomiasis, second-stage disease (off-label use) (Ornidyl only):
Note: For use in patients with second-stage infection with CNS involvement caused by Trypanosoma brucei gambiense (West African).
Combination therapy: IV: 200 mg/kg every 12 hours for 7 days in combination with nifurtimox (Ref).
Monotherapy (alternative therapy): IV: 100 mg/kg every 6 hours for 14 days (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Oral:
eGFR ≥60 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling.
eGFR ≥30 to <60 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling; eflornithine exposure is higher; monitor closely for increased adverse reaction, including hepatotoxicity, hematologic toxicity, and hearing loss.
eGFR <30 mL/minute: Monitor closely for increased adverse reaction, including hepatotoxicity, hematologic toxicity, and hearing loss (eflornithine exposure is higher). Reduce the recommended dose by ~50% as follows (based on BSA):
BSA >1.5 m2: Reduce dose to 384 mg twice daily.
BSA 0.75 to 1.5 m2: Reduce dose to 384 mg in the morning and 192 mg in the evening.
IV (off label): No specific recommendations are available.
Hepatic impairment prior to treatment initiation:
Mild hepatic impairment (bilirubin ≤ ULN and AST > ULN or bilirubin >1 times ULN and any AST): Oral: There are no dosage adjustments provided in the manufacturer's labeling; however, no clinically significant differences in eflornithine pharmacokinetics were noted based on mild hepatic impairment.
Moderate to severe hepatic impairment: Oral: There are no dosage adjustments provided in the manufacturer's labeling.
IV (off label): No specific recommendations are available.
Acute hepatotoxicity during treatment:
AST or ALT ≥10 times ULN: Oral: Withhold eflornithine until recovery to <10 times ULN. If recovery occurs within 7 days of interruption, resume at the same dose. If recovery occurs after 7 days of interruption, resume at the next reduced dose level.
Neuroblastoma, high-risk:
American Society of Clinical Oncology guidelines for appropriate systemic therapy dosing in adults with cancer with a BMI ≥30 kg/m2: Utilize patient's actual body weight for calculation of BSA- or weight-based dosing; manage regimen-related toxicities in the same manner as for patients with a BMI <30 kg/m2; if a dose reduction is utilized due to toxicity, may consider resumption of full, weight-based dosing (or previously tolerated dose level) with subsequent cycles only if dose escalations are allowed in the prescribing information, if contributing underlying factors (eg, hepatic or kidney impairment) are sufficiently resolved, AND if performance status has markedly improved or is considered adequate (Ref).
|
Current eflornithine oral dosage |
Recommended eflornithine oral dosage and schedule for toxicity |
|---|---|
|
768 mg twice daily |
576 mg twice daily |
|
576 mg twice daily |
384 mg twice daily |
|
384 mg twice daily |
192 mg twice daily |
|
192 mg twice daily |
192 mg once daily |
|
192 mg once daily |
If unable to tolerate the minimum dose of 192 mg once daily, permanently discontinue eflornithine. |
|
Adverse reaction |
Severity |
Eflornithine oral dosage modification |
|---|---|---|
|
Hematologic toxicity | ||
|
Anemia |
Hemoglobin <8 g/dL (first occurrence) |
Withhold eflornithine until hemoglobin ≥8 g/dL; resume eflornithine at the same dose. |
|
Hemoglobin <8 g/dL (recurrent) |
Withhold eflornithine until hemoglobin ≥8 g/dL; resume eflornithine at the next reduced dose level. | |
|
Neutropenia |
ANC <500/mm3 |
Withhold eflornithine until ANC ≥500/mm3. Recovery within 7 days of interruption: Resume eflornithine at the same dose. Recovery after 7 days of interruption: Resume eflornithine at the next reduced dose level. |
|
Thrombocytopenia |
Platelets <25,000/mm3 |
Withhold eflornithine until platelets ≥25,000/mm3. Recovery within 7 days of interruption: Resume eflornithine at the same dose. Recovery within 7 to 14 days of interruption: Resume eflornithine at the next reduced dose level. Not recovered within 14 days of interruption: Permanently discontinue eflornithine. |
|
Nonhematologic toxicity | ||
|
GI toxicity (eg, nausea, vomiting, diarrhea) |
Grade 3 |
If symptoms respond to supportive treatment (eg, anti-emetic or anti-diarrheal therapy), continue eflornithine at the same dose. If symptoms do not respond to supportive treatment, withhold eflornithine until recovery to ≤ grade 2; resume eflornithine at the next reduced dose level. |
|
Ototoxicity |
Clinically concerning new or worsening hearing loss compared to baseline audiogram |
Continue eflornithine dosing and repeat audiogram in 3 weeks. Improvement on repeat audiogram: Continue eflornithine at the same dose. Persistent clinically concerning changes on repeat audiogram: Withhold eflornithine for up to 30 days and repeat audiogram. If stable or improved, resume eflornithine at the next reduced dose level. May also require hearing aids and/or eflornithine discontinuation based on severity. |
|
Other adverse reactions |
Grade 3 or 4 |
Withhold eflornithine until recovery to ≤ grade 2; resume eflornithine at the next reduced dose level. |
|
Grade 4 (recurrent) |
Permanently discontinue eflornithine. | |
Refer to adult dosing.
(For additional information see "Eflornithine (United States: Availability of intravenous preparation limited to CDC and WHO distribution programs) (systemic): Pediatric drug information")
African trypanosomiasis (sleeping sickness), caused by Trypanosoma brucei gambiense : Limited data available:
Note: Parenteral product only available in the United States through special distribution programs. Choice of regimen depends on age, weight, and cerebrospinal fluid (CSF) findings; see guidelines for details; alternative agents are generally preferred for first stage disease.
NECT regimen: Children and Adolescents: Ornidyl: IV: 200 mg/kg/dose every 12 hours for 7 days in combination with oral nifurtimox for 10 days. For the NECT-long rescue treatment, continue eflornithine for 14 days (Ref). Note: NECT is preferred over monotherapy.
Monotherapy (alternative regimen): Children and Adolescents: Ornidyl: 100 mg/kg/dose every 6 hours for 14 days (Ref).
Neuroblastoma, high risk: Note: For use in patients who have demonstrated at least a partial response to prior multiagent, multimodality therapy including anti-GD2 immunotherapy.
Children and Adolescents: Iwilfin: Note: Recalculate BSA every 3 months and adjust dose accordingly.
0.25 to <0.5 m2: Oral: 192 mg twice daily.
0.5 to <0.75 m2: Oral: 384 mg twice daily.
0.75 to ≤1.5 m2: Oral: 576 mg twice daily.
>1.5 m2: Oral: 768 mg twice daily.
Dosage adjustment for toxicity:
Neuroblastoma; high-risk: Children ≥1 year and Adolescents: Iwilfin: Oral: If an adverse reaction occurs, dose should be reduced based on current dose. If subsequent adverse reaction occurs, continue dose reductions until reaching the minimum dose; if patient is unable to tolerate the minimum dose then permanently discontinue therapy.
|
Current oral daily dose |
Reduced oral dose for toxicity management |
|---|---|
|
768 mg twice daily |
576 mg twice daily |
|
576 mg twice daily |
384 mg twice daily |
|
384 mg twice daily |
192 mg twice daily |
|
192 mg twice daily |
192 mg once daily |
|
192 mg once daily |
Permanently discontinue therapy if patient unable to tolerate dose. |
|
Adverse reaction |
Severity |
Eflornithine dosage modification |
|---|---|---|
|
Hematologic toxicity | ||
|
Anemia |
Hemoglobin <8 g/dL (first occurrence) |
Withhold eflornithine until hemoglobin ≥8 g/dL; resume eflornithine at the same dose. |
|
Hemoglobin <8 g/dL (recurrent) |
Withhold eflornithine until hemoglobin ≥8 g/dL; resume eflornithine at the next reduced dose level. | |
|
Neutropenia |
ANC <500/mm3 |
Withhold eflornithine until ANC ≥500/mm3. Recovery within 7 days of interruption: Resume eflornithine at the same dose. Recovery after 7 days of interruption: Resume eflornithine at the next reduced dose level. |
|
Thrombocytopenia |
Platelets <25,000/mm3 |
Withhold eflornithine until platelets ≥25,000/mm3. Recovery within 7 days of interruption: Resume eflornithine at the same dose. Recovery within 7 to 14 days of interruption: Resume eflornithine at the next reduced dose level. Not recovered within 14 days of interruption: Permanently discontinue eflornithine. |
|
Nonhematologic toxicity | ||
|
GI toxicity (eg, nausea, vomiting, diarrhea) |
Grade 3 |
If symptoms respond to supportive treatment (eg, anti-emetic or anti-diarrheal therapy), continue eflornithine at the same dose. If symptoms do not respond to supportive treatment, withhold eflornithine until recovery to ≤ grade 2; resume eflornithine at the next reduced dose level. |
|
Ototoxicity |
Clinically concerning new or worsening hearing loss compared to baseline audiogram |
Continue eflornithine dosing and repeat audiogram in 3 weeks. Improvement on repeat audiogram: Continue eflornithine at the same dose. Persistent clinically concerning changes on repeat audiogram: Withhold eflornithine for up to 30 days and repeat audiogram. If stable or improved, resume eflornithine at the next reduced dose level. May also require hearing aids and/or eflornithine discontinuation based on severity. |
|
Other adverse reactions |
Grade 3 or 4 |
Withhold eflornithine until recovery to ≤ grade 2; resume eflornithine at the next reduced dose level. |
|
Grade 4 (recurrent) |
Permanently discontinue eflornithine. | |
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Altered kidney function: Children and Adolescents:
Neuroblastoma: Oral: Iwilfin:
eGFR ≥60 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling.
eGFR 30 to <60 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling; eflornithine exposure is higher; monitor closely for increased adverse reaction, including hepatotoxicity, hematologic toxicity, and hearing loss.
eGFR <30 mL/minute: Reduce the recommended dose by ~50% as follows. Monitor closely for increased adverse reaction, including hepatotoxicity, hematologic toxicity, and hearing loss.
0.25 to <0.5 m2: Oral: 192 mg once daily.
0.5 to <0.75 m2: Oral: 192 mg twice daily.
0.75 to ≤1.5 m2: Oral: 384 mg in the morning and 192 mg in the evening.
>1.5 m2: Oral: 384 mg twice daily.
African trypanosomiasis (sleeping sickness): IV: Ornidyl: There are no specific dosage adjustments are available; however, based on experience with oral therapy for neuroblastoma, dosage adjustment is likely necessary.
Neuroblastoma: Oral: Iwilfin:
Children ≥1 year and Adolescents:
Baseline hepatic impairment:
Mild hepatic impairment (bilirubin ≤ ULN and AST > ULN or bilirubin >1 times ULN and any AST): Oral: There are no dosage adjustments provided in the manufacturer's labeling; however, no clinically significant differences in eflornithine pharmacokinetics were noted based on mild hepatic impairment.
Moderate to severe hepatic impairment: Oral: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Acute hepatotoxicity during treatment:
AST or ALT ≥10 times ULN: Oral: Withhold eflornithine until recovery to <10 times ULN. If recovery occurs within 7 days of interruption, resume at the same dose. If recovery occurs after 7 days of interruption, resume at the next reduced dose level.
|
Current oral daily dose |
Reduced oral dose for toxicity management |
|---|---|
|
768 mg twice daily |
576 mg twice daily |
|
576 mg twice daily |
384 mg twice daily |
|
384 mg twice daily |
192 mg twice daily |
|
192 mg twice daily |
192 mg once daily |
|
192 mg once daily |
Permanently discontinue therapy if patient unable to tolerate dose. |
African trypanosomiasis (sleeping sickness): IV: Ornidyl: No specific recommendations are available.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported for the oral formulation in children and adolescents.
>10%:
Gastrointestinal: Diarrhea (15%; grade 3: 4%), vomiting (11%; grade 3: 1%)
Ophthalmic: Conjunctivitis (11%)
Otic: Otitis media (32%)
Respiratory: Allergic rhinitis (11%), cough (15%), pneumonia (12%), sinusitis (13%), upper respiratory tract infection (11%)
Miscellaneous: Fever (11%)
1% to 10%:
Dermatologic: Alopecia (<5%), skin infection (7%), skin rash (<5%)
Endocrine & metabolic: Decreased serum glucose (2%), decreased serum potassium (2%), decreased serum sodium (2%), increased serum glucose (1%), increased serum potassium (1%)
Genitourinary: Urinary tract infection (6%)
Hematologic & oncologic: Decreased hemoglobin (5%; grade 3: 2%), decreased neutrophils (9%; grades 3/4: 8%), decreased platelet count (1%), decreased white blood cell count (2%)
Hepatic: Increased serum alanine aminotransferase (9%), increased serum alkaline phosphatase (5%), increased serum aspartate aminotransferase (8%)
Neuromuscular & skeletal: Limb pain (<5%)
Otic: Hearing loss (7%)
There are no contraindications listed in the manufacturer's labeling.
Concerns related to adverse effects:
• Hepatotoxicity: Grades 3 or 4 elevations of AST, ALT, and bilirubin have been observed in patients treated with eflornithine, leading to dosage modification or discontinuation in a small percentage of patients.
• Myelosuppression: Eflornithine may cause myelosuppression, including grade 3 anemia, grades 3 or 4 neutropenia, and grades 3 or 4 thrombocytopenia. Febrile neutropenia and bone marrow failure occurred rarely.
• Ototoxicity: Eflornithine may cause hearing loss. In the clinical study, more than three-quarters of treated patients had an abnormal audiogram at baseline, with new or worsening hearing loss occurring in 12% of patients (including worsening to grades 3 or 4 hearing loss and tinnitus in one patient). New or worsening hearing loss during treatment with eflornithine led to new hearing aid use, dosage modifications, and dosage discontinuation in some patients. Among all patients that experienced hearing loss with eflornithine, ~10% resolved to baseline, and of those who had dosage modification, approximately two-thirds of patients improved or had resolution to baseline.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral, as hydrochloride:
Iwilfin: 192 mg [contains corn starch]
No
Tablets (Iwilfin Oral)
192 mg (per each): $113.39
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Eflornithine tablets are available through a specialty pharmacy. Information from the manufacturer may be found at https://hcp.iwilfin.com/access-resources.
Eflornithine injectable is donated to the World Health Organization (WHO) by the manufacturer. In the United States, eflornithine injection is available through the CDC for treatment of second-stage African trypanosomiasis (caused by Trypanosoma brucei gambiense) with CNS involvement. Further information may be found on the WHO website at https://www.who.int/health-topics/human-african-trypanosomiasis or by contacting the CDC Drug Service (404-639-3670). Additional information from the CDC is available at https://www.cdc.gov/laboratory/drugservice/formulary.html.
Oral: Administer with or without food; tablets may be swallowed whole, chewed, or crushed.
Crushed tablets preparation: For patients with difficulty swallowing tablets, eflornithine may be chewed, or crushed and mixed with 2 tablespoons of soft food or liquid. Visually confirm the entire contents of the dose are administered; if crushed tablet particles remain, may mix with an additional small volume (eg, no more than 1 ounce [30 mL]) of soft food or liquid. Discard crushed preparation if not administered within 1 hour.
IV (off label): Administer IV only; do not administer IM. Dilute prior to use and infuse over 120 minutes; replace IV catheter at least every 48 hours (Ref).
Oral: Administer with or without food; tablets may be swallowed whole, chewed, or crushed. If dose is vomited, an additional dose should not be administered; continue with next scheduled dose.
Administration in soft food or liquid: For patients with difficulty swallowing tablets, eflornithine may be chewed, or crushed and mixed with 2 tablespoons of soft food or liquid. Visually confirm the entire contents of the dose are administered; if crushed tablet particles remain, may mix with an additional small volume (eg, no more than 1 ounce [30 mL]) of soft food or liquid. Discard crushed preparation if not administered within 1 hour.
Parenteral: IV: Administer diluted solution by IV infusion over 2 hours (Ref).
This medication is not on the NIOSH (2024) list; however, it may meet the criteria for a hazardous drug. Eflornithine may cause developmental toxicity.
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2023; NIOSH 2024; USP-NF 2020).
Note: Facilities may perform risk assessment of some hazardous drugs to determine if appropriate for alternative handling and containment strategies (USP-NF 2020). Refer to institution-specific handling policies/procedures.
Neuroblastoma, high-risk: To reduce the risk of relapse of high-risk neuroblastoma in adult and pediatric patients who have demonstrated at least a partial response to prior multiagent, multimodality therapy including anti-GD2 immunotherapy (Iwilfin tablets only).
West African trypanosomiasis, second-stage disease
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes (chemotherapeutic agent, parenteral and oral) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Acute Care, Community/Ambulatory Care, and Long-Term Care Settings).
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
5-Aminosalicylic Acid Derivatives: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
Antithyroid Agents: Myelosuppressive Agents may increase neutropenic effects of Antithyroid Agents. Risk C: Monitor
BCG (Intravesical): Myelosuppressive Agents may decrease therapeutic effects of BCG (Intravesical). Myelosuppressive Agents may increase adverse/toxic effects of BCG (Intravesical). Risk X: Avoid
Chloramphenicol (Ophthalmic): May increase adverse/toxic effects of Myelosuppressive Agents. Risk C: Monitor
Chloramphenicol (Systemic): Myelosuppressive Agents may increase myelosuppressive effects of Chloramphenicol (Systemic). Risk X: Avoid
Cladribine: May increase myelosuppressive effects of Myelosuppressive Agents. Risk X: Avoid
CloZAPine: Myelosuppressive Agents may increase adverse/toxic effects of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor
Deferiprone: Myelosuppressive Agents may increase neutropenic effects of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider Therapy Modification
Fexinidazole: Myelosuppressive Agents may increase myelosuppressive effects of Fexinidazole. Risk X: Avoid
Linezolid: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
Olaparib: Myelosuppressive Agents may increase myelosuppressive effects of Olaparib. Risk C: Monitor
Promazine: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
Ropeginterferon Alfa-2b: Myelosuppressive Agents may increase myelosuppressive effects of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider Therapy Modification
Verify pregnancy status prior to initiating treatment in patients who could become pregnant.
Patients who may become pregnant should use effective contraception during therapy and for 1 week after the last dose of eflornithine. Patients with partners who could become pregnant should also use effective contraception during therapy and for 1 week after the last eflornithine dose.
Based on the mechanism of action and data from animal reproduction studies, in utero exposure to eflornithine may cause fetal harm. Embryolethality was observed following oral administration to pregnant rats and rabbits during the period of organogenesis with doses equivalent to the recommended human dose (based on BSA).
Outcome data related to systemic eflornithine are limited following use as part of combination therapy for the treatment of West African trypanosomiasis (Ref).
It is not known if eflornithine is present in breast milk.
Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer during therapy and for 1 week after the last dose of eflornithine.
Outcome data related to systemic eflornithine in breastfeeding patients are limited following use as part of combination therapy for the treatment of West African trypanosomiasis (Ref).
Oral: Monitor CBC (prior to therapy and periodically during treatment); liver function (ALT, AST, and total bilirubin) tests (prior to therapy, every month for the first 6 months of treatment, then every 3 months or as clinically indicated; monitor more frequently in patients with transaminase or bilirubin elevations). Obtain baseline audiogram; repeat audiogram at 6-month intervals or as clinically indicated to monitor hearing loss. Verify pregnancy status prior to initiating treatment in patients who could become pregnant. Monitor for signs/symptoms of hepatotoxicity and hearing loss. Monitor closely for increased adverse reaction, including hepatotoxicity, hematologic toxicity, and hearing loss in patients with kidney function impairment. Monitor adherence.
The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (Ref) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
IV: CBC with platelet counts. Monitor for signs/symptoms of hearing loss.
Eflornithine exerts antitumor and antiprotozoal effects through specific, irreversible inhibition of the enzyme ornithine decarboxylase (ODC). ODC is the rate-limiting enzyme in the biosynthesis of polyamines in nucleated cells. Polyamines are necessary for the synthesis of DNA, RNA, and proteins and are, therefore, necessary for cell growth and differentiation. Mammalian cells depend on ornithine decarboxylase to produce polyamines.
In the treatment of neuroblastoma, ODC inhibition by eflornithine additionally reverses the effects of the LIN28/Let7 metabolic pathway (involved in cancer stem cell regulation and glycolytic metabolism), decreasing expression of oncogenic drivers MYCN and LIN28B (Ref). In vitro, eflornithine suppressed neurosphere formation in neuroblastoma cell lines, regardless of MYCN amplification (Ref).
Distribution: Oral: Vd: 24.3 L.
Half-life elimination: Oral: 3.5 hours; IV: 1.5 to 5 hours (Ref).
Time to peak: Oral: 3.5 hours.
Excretion: Clearance: Oral: 5.3 L/hour.
