Usage
- Eflornithine is prescribed for two main purposes:
- Treatment of second-stage West African trypanosomiasis (sleeping sickness) caused by Trypanosoma brucei gambiense. This parasitic infection affects the central nervous system. Intravenous administration is used for this purpose.
- Reduction of unwanted facial hair growth (hirsutism) in women. Topical cream formulation is used for this indication.
- Pharmacological classification: Enzyme inhibitor (ornithine decarboxylase inhibitor), antiprotozoal agent (for sleeping sickness).
- Mechanism of action: Eflornithine irreversibly inhibits ornithine decarboxylase (ODC), an enzyme crucial for polyamine biosynthesis. Polyamines are essential for cell division and growth. By inhibiting ODC, eflornithine slows the rate of hair growth and interferes with the proliferation of trypanosomes.
Alternate Names
- Generic name: Eflornithine hydrochloride
- Brand names: Vaniqa (topical cream), Ornidyl (injectable)
- Other names: DFMO (difluoromethylornithine)
How It Works
- Pharmacodynamics: Eflornithine inhibits ornithine decarboxylase, which leads to a depletion of polyamines, inhibiting cell growth and division. This leads to slowed hair follicle growth in topical applications and suppression of trypanosome replication in intravenous application.
- Pharmacokinetics (Topical): Minimally absorbed systemically following topical application.
- Pharmacokinetics (Intravenous): Peak plasma concentrations reached in approximately 4 hours. Elimination half-life is 3-4 hours. Primarily excreted unchanged in urine.
- Mode of action: Irreversible inhibition of ornithine decarboxylase.
- Receptor binding/enzyme inhibition/neurotransmitter modulation: Suicide inhibition of ornithine decarboxylase.
- Elimination pathways: Primarily renal excretion.
Dosage
Standard Dosage
Adults (Topical):
- Apply a thin layer of eflornithine cream 13.9% to the affected areas of the face and adjacent skin under the chin twice daily, at least 8 hours apart.
- Maximum dose: Up to 30 grams per month.
Children (Topical):
- Safety and efficacy not established in children under 18 years of age for topical use.
Adults (Intravenous - for West African trypanosomiasis):
- 100 mg/kg every 6 hours intravenously for 14 days.
Children (Intravenous - for West African trypanosomiasis):
- Under 12 years: 150 mg/kg every 6 hours intravenously for 14 days.
- 12 years and over: 100 mg/kg every 6 hours intravenously for 14 days.
Special Cases:
- Elderly Patients: No dose adjustment necessary for topical or intravenous use.
- Patients with Renal Impairment: Caution advised in patients with severe renal impairment for both formulations, as eflornithine is primarily renally excreted.
- Patients with Hepatic Dysfunction: No specific dose adjustment recommendations. Exercise caution.
- Patients with Comorbid Conditions: No specific dose adjustments indicated. However, consider individual patient characteristics.
Clinical Use Cases The listed clinical use cases apply to situations encountered during intravenous eflornithine administration for West African sleeping sickness. These scenarios are not applicable to topical eflornithine cream usage. Topical eflornithine cream is solely used for the reduction of unwanted facial hair.
- Intubation, Surgical Procedures, Mechanical Ventilation, Intensive Care Unit (ICU) Use, Emergency Situations: Dosage adjustment may be needed depending on the specific situation and the patient’s condition during intravenous eflornithine administration for West African sleeping sickness.
Dosage Adjustments
Dosage adjustments are necessary for intravenous eflornithine for patients with impaired renal function. For topical eflornithine cream, no formal dose adjustments are provided, but practitioners should exercise clinical judgment in patients with renal or hepatic impairments.
Side Effects
Common Side Effects (Topical):
- Acne
- Folliculitis (ingrown hairs)
- Burning sensation
- Stinging
- Dry skin
- Itching
- Erythema
- Pruritus
- Temporary hair loss
Common Side Effects (Intravenous):
- Diarrhea
- Nausea
- Vomiting
- Abdominal pain
- Anorexia
- Seizures
- Anemia
- Leukopenia
- Thrombocytopenia
- Headache
- Dizziness
- Peripheral neuropathy
- Hearing loss
Rare but Serious Side Effects:
- Severe skin irritation (topical)
- Hepatotoxicity (intravenous)
- Bone marrow suppression (intravenous)
- Severe allergic reactions
Long-Term Effects:
- Hearing loss (intravenous)
Adverse Drug Reactions (ADR):
- Stevens-Johnson Syndrome (rare)
- Toxic epidermal necrolysis (rare)
- Anaphylaxis (rare)
Contraindications
- Topical: Hypersensitivity to eflornithine hydrochloride or any of the excipients.
- Intravenous: Hypersensitivity to eflornithine hydrochloride.
Drug Interactions
- Limited information available about drug interactions for topical eflornithine. No clinically significant interactions are currently known. For other forms of eflornithine, interactions may occur.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: C (for intravenous use). Not assigned for topical.
- Fetal risks: Topical: Minimal risk as limited systemic absorption is expected.
Intravenous: Potential for fetotoxicity and teratogenicity. Use with caution if benefits outweigh risks.
- Breastfeeding: Not recommended for intravenous administration during treatment and for 1 week after the last dose. Topical use is generally considered safe as minimal systemic absorption is expected.
Drug Profile Summary
- Mechanism of Action: Irreversible inhibition of ornithine decarboxylase.
- Side Effects (Topical): Acne, folliculitis, burning, stinging, dry skin, itching, redness.
- Side Effects (Intravenous): Diarrhea, nausea, vomiting, seizures, anemia, leukopenia, thrombocytopenia, hearing loss.
- Contraindications: Hypersensitivity to eflornithine.
- Drug Interactions: Limited data available.
- Pregnancy & Breastfeeding: Topical: Minimal risk expected due to low systemic absorption. Intravenous: Use with caution during pregnancy. Not recommended while breastfeeding.
- Dosage (Topical): Apply a thin layer twice daily, 8 hours apart.
- Dosage (Intravenous - for West African trypanosomiasis): 100 mg/kg every 6 hours IV for 14 days (adults and children over 12 years).
- Monitoring Parameters: (For intravenous use): Complete blood counts, liver function tests, audiometry.
Popular Combinations
- Nifurtimox: Used in combination with intravenous eflornithine for the treatment of late-stage West African trypanosomiasis.
Precautions
- General Precautions: Skin irritation may occur with topical use.
- Specific Populations:
- Pregnant Women: Topical: Minimal risk expected due to low systemic absorption. Intravenous: Potential risk to fetus; weigh risks and benefits.
- Breastfeeding Mothers: Topical: Generally safe. Intravenous: Not recommended.
- Children & Elderly (Topical): Safety and efficacy for topical use not established in children under 18. No dose adjustments are necessary for the elderly.
- Children & Elderly (Intravenous): Dosage adjustments necessary for children under 12 years. No dose adjustments are needed for elderly patients for intravenous use.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for topical eflornithine?
A: Apply a thin layer of eflornithine hydrochloride cream 13.9% to the affected areas of the face and adjacent skin under the chin twice daily, at least 8 hours apart.
Q2: How long does it take to see results with topical eflornithine?
A: Improvement may be noticed within 8 weeks of starting treatment, but continued treatment is necessary to maintain beneficial effects.
Q3: Is topical eflornithine a permanent hair removal method?
A: No. Hair growth will return to pre-treatment levels within eight weeks following discontinuation of treatment. Patients may need to continue their usual hair removal methods while using eflornithine.
Q4: What are the common side effects of topical eflornithine?
A: Common side effects include acne, folliculitis, burning, stinging, dry skin, itching, and redness.
Q5: Can topical eflornithine be used during pregnancy or while breastfeeding?
A: Topical eflornithine is generally considered safe during pregnancy and breastfeeding due to its low systemic absorption. However, intravenous eflornithine carries risks during pregnancy and is not recommended while breastfeeding.
Q6: What is the role of eflornithine in treating sleeping sickness?
A: Intravenous eflornithine is used to treat the second stage of West African trypanosomiasis (sleeping sickness) caused by Trypanosoma brucei gambiense.
Q7: What is the mechanism of action of eflornithine?
A: Eflornithine irreversibly inhibits the enzyme ornithine decarboxylase (ODC), which is involved in polyamine synthesis. This leads to the inhibition of cell growth and division, affecting the rate of hair growth or the proliferation of trypanosomes.
Q8: What are the contraindications to eflornithine use?
A: Known hypersensitivity to eflornithine or any of its components is a contraindication.
Q9: How should topical eflornithine cream be applied?
A: Apply a thin layer to clean, dry skin on affected areas of the face and under the chin, twice daily at least 8 hours apart. Avoid washing the treated area for at least 4 hours after application.
Q10: What are some important considerations for patient counseling regarding eflornithine use?
A: Patients should be informed that topical eflornithine is not a depilatory and does not permanently remove hair. It is important to manage expectations and inform patients that continued use is needed to maintain the reduction in hair growth. Patients using the intravenous formulation should be educated on the potential for serious adverse effects, including bone marrow suppression, hearing loss, and seizures, and the importance of reporting any new or worsening symptoms promptly.
