Eflornithine Hydrochloride

Approved Indications:

• Facial Hirsutism in Women:
• Topical Eflornithine Hydrochloride 13.9% cream is indicated for the reduction of unwanted facial hair growth in women. It is used as an adjunct to hair removal techniques (e.g., shaving, plucking).
• Human African Trypanosomiasis (HAT):
• Parenteral Eflornithine (IV formulation) is used in the treatment of second-stage Trypanosoma brucei gambiense (West African sleeping sickness), typically in combination with nifurtimox.

Off-label/Clinically Accepted Uses:

• None well-established beyond approved uses. However, research continues in dermatology and parasitology for broader applications.

For Facial Hirsutism (Topical Cream 13.9%):

• Adults (Women only):
• Apply a thin layer of the cream to affected facial areas twice daily, at least 8 hours apart.
• Apply after hair removal methods (e.g., shaving, plucking); do not wash treated area for at least 4 hours after application.
• Children:
• Not recommended under 12 years of age due to lack of safety and efficacy data.
• Elderly:
• No dosage adjustment required; use with caution due to potential skin sensitivity.
• Renal/Hepatic Impairment:
• No adjustment required for topical use due to minimal systemic absorption.

For Human African Trypanosomiasis (Parenteral Use):

• Adults and Children:
• 100 mg/kg IV every 6 hours for 14 days.
• Administer by slow intravenous infusion over 60 minutes.
• Often used in combination with oral nifurtimox in WHO-endorsed regimens.
• Renal Impairment:
• Dosage may require adjustment in severe renal dysfunction (for IV use); monitor closely.

Eflornithine is an irreversible inhibitor of ornithine decarboxylase (ODC), a rate-limiting enzyme in polyamine biosynthesis. By inhibiting ODC, it reduces intracellular polyamines (putrescine, spermidine, and spermine) required for cell proliferation and differentiation. In facial hirsutism, this slows down the rate of hair growth at the follicular level. In HAT, polyamine depletion in Trypanosoma brucei interferes with parasite cell growth and division, leading to parasitic death, particularly effective in the CNS phase of the disease.

Topical Eflornithine:

• Absorption:
• <1% systemically absorbed when applied to intact skin.
• Distribution, Metabolism, Elimination:
• Negligible systemic exposure; no significant data applicable.

IV Eflornithine (for HAT):

• Absorption: Not applicable (IV use).
• Distribution: Widely distributed, including penetration into the cerebrospinal fluid.
• Metabolism: Not extensively metabolized.
• Half-life: 3–5 hours.
• Excretion: Primarily excreted unchanged in the urine (>80%); renal clearance is the main elimination pathway.

• Pregnancy:
• Topical Use: Category C (FDA). Animal studies have shown adverse effects, but human data are limited. Use only if clearly needed.
• IV Use: Limited data; use only if potential benefits outweigh risks. Often essential in treating life-threatening sleeping sickness in pregnant women.
• Lactation:
• Unknown if excreted in human milk. Due to minimal absorption with topical use, risk to breastfed infants is considered low. Avoid application on or near the breast.
• For IV use, use caution and monitor infant for potential adverse effects if breastfeeding is continued.
• General:
• Caution advised during pregnancy and lactation; clinical use should weigh risks and benefits.

• Primary Class:
• Topical Eflornithine: Dermatological agent for hair growth reduction
• IV Eflornithine: Antiparasitic agent
• Subclass:
• Ornithine decarboxylase inhibitor (polyamine synthesis inhibitor)

• Known hypersensitivity to eflornithine or any formulation component.
• Use on broken, inflamed, or infected skin (topical use).
• Pediatric use in facial hirsutism.
• Severe renal impairment (IV use), unless benefit outweighs risk.

• Skin Reactions (Topical):
• May cause stinging, burning, redness, folliculitis, or acne at the application site.
• Discontinue if severe irritation occurs.
• Slow Onset (Topical):
• Cosmetic improvement may take 8 weeks or longer; effect is not permanent. Hair returns to pretreatment levels after discontinuation.
• Infectious Risks (IV):
• Neutropenia, anemia, and thrombocytopenia may occur; monitor CBC regularly.
• Monitor renal and hepatic function during therapy.
• CNS Toxicity (IV):
• May cause seizures, confusion, or hearing loss in rare cases.

Topical Use:

• Common:
• Acne, redness, tingling, stinging, burning, skin dryness.
• Less Common:
• Folliculitis, rash, pruritus.

IV Use (Systemic):

• Common:
• Bone marrow suppression (anemia, neutropenia, thrombocytopenia)
• Diarrhea, nausea, vomiting
• Seizures, headache, hearing loss
• Fever, rash
• Serious (Rare):
• Severe neutropenia or thrombocytopenia
• Irreversible hearing impairment
• Allergic reactions, including anaphylaxis (rare)

Topical:

• No known significant drug-drug, food, or alcohol interactions due to minimal systemic absorption.

IV (Systemic):

• May potentiate hematologic toxicity when used with other bone marrow suppressive agents.
• Risk of nephrotoxicity increases if used with nephrotoxic drugs (e.g., aminoglycosides).
• Avoid concurrent use with medications known to lower seizure threshold.

Enzyme Systems:

• Eflornithine does not significantly inhibit or induce CYP450 enzymes.

• WHO Guidelines:
• Endorses eflornithine in combination with nifurtimox for stage-2 HAT as the preferred regimen due to superior efficacy and tolerability.
• No major recent changes in dosing or indications for topical use.
• Continued emphasis on the importance of long-term adherence and expectation management in facial hirsutism.

Topical Cream (13.9%):

• Store at 20°C to 25°C (68°F to 77°F).
• Protect from light and moisture.
• Do not freeze.
• Keep tightly closed and out of reach of children.

IV Formulation:

• Store vials at 2°C to 8°C (36°F to 46°F).
• Protect from light.
• Diluted solution must be used within a specified timeframe (typically within 24 hours if refrigerated).
• Do not freeze.