eflornithine (systemic)

Inhibits ornithine decarboxylase, which is the rate-limiting enzyme in the biosynthesis of polyamines. Polyamines are necessary for cell growth and differentiation because they are required for the synthesis of DNA, RNA, and proteins. Additionally, inhibition of ornithine decarboxylase reverses the effects of the LIN28/Let7 metabolic pathway, which reduces expression of certain proteins (involved in cancer stem cell regulation and glycolytic metabolism), decreasing expression of the oncogenic drivers MYCN and LIN28B.

Therapeutic effects:

Reduction in disease progression, relapse, secondary cancer, or death.

Pharmacokinetics ⬆ ⬇

Absorption: Extent of absorption following oral administration unknown.

Distribution: Well distributed to tissues.

Metabolism/Excretion: Unknown.

Half-Life: 3.5 hr.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	3.5 hr	unknown

Contraind./Precautions ⬆ ⬇

Contraindicated in:

OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

Severe renal impairment (↓ dose);
Rep: Women of reproductive potential and men with female partners of reproductive potential.

Adv. Reactions/Side Effects ⬆ ⬇

Derm: alopecia, rash, skin infection

EENT: conjunctivitis, otitis media, sinusitis, hearing loss

Endo: hyperglycemia, hypoglycemia

F and E: hyperkalemia, hypokalemia, hyponatremia

GI: diarrhea, vomiting, ↑liver enzymes, HEPATOTOXICITY

GU: urinary tract infection

Hemat: anemia, leukopenia, NEUTROPENIA, THROMBOCYTOPENIA

MS: pain

Resp: allergic rhinitis, cough, pneumonia

Misc: fever

Interactions ⬆ ⬇

Drug-drug:

None reported.

Route/Dosage ⬆ ⬇

PO (Adults and Children body surface area (BSA) >1.5 m²): 768 mg twice daily for 2 yr or until disease recurrence or unacceptable toxicity.
PO (Adults and Children BSA 0.75–1.5 m²): 576 mg twice daily for 2 yr or until disease recurrence or unacceptable toxicity.
PO (Adults and Children BSA 0.5–<0.75 m²): 384 mg twice daily for 2 yr or until disease recurrence or unacceptable toxicity.
PO (Adults and Children BSA 0.25–<0.5 m²): 192 mg twice daily for 2 yr or until disease recurrence or unacceptable toxicity.

Renal Impairment

PO (Adults and Children BSA >1.5 m²): CCr <30 mL/min: 384 mg twice daily for 2 yr or until disease recurrence or unacceptable toxicity.

Renal Impairment

PO (Adults and Children BSA 0.75–1.5 m²): CCr <30 mL/min: 384 mg in the morning and 192 mg in the evening for 2 yr or until disease recurrence or unacceptable toxicity.

Renal Impairment

PO (Adults and Children BSA 0.5–<0.75 m²): CCr <30 mL/min: 192 mg twice daily for 2 yr or until disease recurrence or unacceptable toxicity.

Renal Impairment

PO (Adults and Children BSA 0.25–<0.5 m²): CCr <30 mL/min: 192 mg once daily for 2 yr or until disease recurrence or unacceptable toxicity.

Availability ⬆ ⬇

Assessment ⬆ ⬇

Obtain a baseline audiogram before starting therapy and then every 6 mo or as clinically indicated. May cause ototoxicity. If new or worsening hearing loss from baseline, continue dose and repeat audiogram in 3 wk. If improved, continue at same dose. If clinically concerning changes persist, hold >30 days and repeat audiogram. If stable or improved, resume at next ↓ dose level.
Monitor for signs and symptoms of myelosuppression (fever, fatigue, uncontrolled bleeding).
Monitor for signs and symptoms of hepatotoxicity (jaundice, dark-colored urine, stomach pain).
Monitor for nausea, vomiting, and diarrhea. If Grade 3 nausea/vomiting/diarrhea occurs, if symptoms respond to antiemetic or antidiarrheal therapy, continue at same dose. If symptoms do not respond to supportive treatment, hold until recovery to Grade ≤2; then resume at next ↓ dose level.
Monitor for other adverse reactions (infections, respiratory disorders, pyrexia). If Grade 3 or 4 adverse reactions occur, hold until recovery to Grade ≤2; then resume at next ↓ dose level. If recurrent Grade 4 adverse reactions occur, permanently discontinue eflornithine.

Lab Test Considerations:

Verify negative pregnancy test before starting therapy.
Monitor CBC with differential before and periodically during therapy. May cause anemia, neutropenia, and thrombocytopenia.
- If 1st occurrence Hgb<8 g/dL, hold dose until ≥8 g/dL; then resume at same dose. If recurrent Hgb <8 g/dL, hold until ≥8 g/dL; then resume at next ↓ dose level.
- If ANC <500 mm², hold dose until ANC ≥500 mm². If recovery <7 days, resume at same dose. If recovery >7 days, resume at next ↓ dose level.
- If platelet count <25,000/mm³, hold dose until platelet count ≥25,000/mm³. If recovery <7 days, resume at same dose. If recovery within 7–14 days, resume at next ↓ dose level. If no recovery within 14 days, permanently discontinue eflornithine.
Monitor electrolytes. May cause hypokalemia and hyopnatremia.
May ↑ ALT and AST and cause hepatotoxicity. Monitor ALT, AST, and total bilirubin at baseline, every mo for 1st 6 mo, and then once every 3 mo or as clinically indicated. If AST or ALT ≥10 times upper limit of normal (ULN), hold dose until recovery to <10 times ULN. If recovery <7 days, resume at same dose. If recovery >7 days, resume at next ↓ dose level.

Implementation ⬆ ⬇

High Alert: 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 strategies.
PO: Administer twice daily with or without food. Tablets may be swallowed whole, chewed, or crushed and mixed with soft food or liquid. If any crushed tablet particles remain in container, mix with 30 mL of soft food or liquid. Discard crushed tablet after 1 hr.
Dose Modifications for Adverse Reactions: Current dose 768 mg twice daily:↓ to 576 mg twice daily. Current dose 576 mg twice daily:↓ to 384 mg twice daily. Current dose 384 mg twice daily:↓ to 192 mg twice daily. Current dose 192 mg twice daily:↓ to 192 mg once daily. If unable to tolerate 192 mg once daily, permanently discontinue eflornithine.

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of medication to patient. Advise patient to read Patient Information before starting therapy. Advise to take as directed. If a dose is missed and it is <7 hr until next dose, skip dose, and take at normal time. Do not take two doses at the same time or extra doses.
Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional before taking other medications.
Advise patient to notify a health care professional if signs and symptoms of hepatotoxicity and/or myelosuppression occur.
Rep: May cause fetal harm. Advise women of reproductive potential to use effective contraception during therapy and for 1 wk after last dose. Advise women not to breastfeed during therapy and for 1 wk after last dose.

Evaluation/Desired Outcomes ⬆ ⬇

Reduction in disease progression, relapse, secondary cancer, or death.

US Brand Names ⬆ ⬇

Code ⬆

NDC Code

51767- CoreRx, Inc.
- 51767-150-
  - 51767-150-01- 17000 TABLET in 1 DRUM (51767-150-01)

54245- SciAnda (Changshu) Pharmaceuticals, Ltd.
- 54245-3110-
  - 54245-3110-0- 70 kg in 1 BAG (54245-3110-0)

65129- ScinoPharm Taiwan Ltd.
- 65129-3110-
  - 65129-3110-0- 60 kg in 1 BAG (65129-3110-0)

73377- AX Pharmaceutical Corp
- 73377-257-
  73377-257-01- 50 g in 1 JAR (73377-257-01)

73377- AX Pharmaceutical Corp
- 73377-257-
  73377-257-02- 500 g in 1 JAR (73377-257-02)

73377- AX Pharmaceutical Corp
- 73377-257-
  73377-257-03- 1000 g in 1 JAR (73377-257-03)

73377- AX Pharmaceutical Corp
- 73377-257-
  73377-257-04- 980 g in 1 JAR (73377-257-04)

73377- AX Pharmaceutical Corp
- 73377-257-
  73377-257-05- 100 g in 1 JAR (73377-257-05)

73377- AX Pharmaceutical Corp
- 73377-257-
  73377-257-06- 993 g in 1 JAR (73377-257-06)

73377- AX Pharmaceutical Corp
- 73377-257-
  73377-257-07- 25 g in 1 JAR (73377-257-07)

73377- AX Pharmaceutical Corp
- 73377-257-
  73377-257-08- 49 g in 1 JAR (73377-257-08)

73377- AX Pharmaceutical Corp
- 73377-257-
  73377-257-09- 960 g in 1 JAR (73377-257-09)

78670- USWM, LLC
- 78670-150- iwilfin
  78670-150-01- 1 BOTTLE in 1 CARTON (78670-150-01) / 100 TABLET in 1 BOTTLE

82160- Pella Pharmaceuticals Co. Ltd
- 82160-125- Florexa
  - 82160-125-01- 1 TUBE in 1 CARTON (82160-125-01) / 30 g in 1 TUBE

section name header

Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇

Time/Action Profile ⬆ ⬇

Contraind./Precautions ⬆ ⬇

Adv. Reactions/Side Effects ⬆ ⬇

Interactions ⬆ ⬇

Route/Dosage ⬆ ⬇

Availability ⬆ ⬇

Assessment ⬆ ⬇

Implementation ⬆ ⬇

Patient/Family Teaching ⬆ ⬇

Evaluation/Desired Outcomes ⬆ ⬇

US Brand Names ⬆ ⬇

Code ⬆