Eflornithine

D11A - Other dermatological preparations ATC D11AX16 Small molecule approved 1990 Oral Parenteral Topical

JFDA label: Florexa Cream

Mechanism of Action

Cream: Eflornithine inhibits the enzyme ornithine decarboxylase (ODC) which inhibits cell division and synthetic functions and thereby affects the rate of hair growth. Injection: Eflornithine exerts antitumor and antiprotozoal effects through specific, irreversible (“suicide”) inhibition of the enzyme ornithine decarboxylase (ODC). ODC is the rate-limiting enzyme in the biosynthesis of putrescine, spermine, and spermidine, the major polyamines in nucleated cells. Polyamines are necessary for the synthesis of DNA, RNA, and proteins and are, therefore, necessary for cell growth and differentiation. Although many microorganisms and higher plants are able to produce polyamines from alternate biochemical pathways, all mammalian cells depend on ornithine decarboxylase to produce polyamines. Ef

Indications

Approved

Facial hair reduction

Off-label

Meningoencephalitic stage of Trypanosoma brucei gambiense infection (sleeping sickness)

Contraindications

Source: Lexicomp

Hypersensitivity to eflornithine or any component of the formulation Absolute

Adverse Reactions

Very Common >10%Common 1–10%Uncommon 0.1–1% Rare 0.01–0.1%Very Rare <0.01%Not Known

Cardiac disorders (6)

Very Common Cardiac arrhythmia · chest pain · hypertension

Common Edema · hypotension · shock

Nervous system disorders (14)

Very Common dizziness · Headache

Common amnesia · anxiety · ataxia · coma · confusion · depression · hallucination · Insomnia · lethargy · peripheral neuropathy · seizure · tingling of skin

Hepatobiliary disorders (2)

Common Abnormal bilirubin levels · increased serum transaminases

Renal and urinary disorders (4)

Common change in creatinine · Urinary frequency · urinary incontinence · urinary urgency

Blood and lymphatic system disorders (4)

Very Common Neutropenia

Common Anemia · leukopenia · thrombocytopenia

Metabolism and nutrition disorders (1)

Common Dehydration

Gastrointestinal disorders (11)

Very Common Abdominal pain · anorexia · diarrhea · nausea · vomiting

Common constipation · dysgeusia · Dyspepsia · Dysphagia · hiccups · xerostomia

Skin and subcutaneous tissue disorders (10)

Very Common Pruritus · skin rash

Common alopecia · burning sensation of skin · erythema · folliculitis · ingrown hair · skin irritation · Stinging of the skin · xeroderma

Musculoskeletal and connective tissue disorders (4)

Very Common Arthralgia · myalgia · weakness

Common Tremor

Ear and labyrinth disorders (1)

Common Inner ear disturbance

Infections and infestations (1)

Very Common Infection

General disorders and administration site conditions (3)

Very Common Fever · Injection site reaction

Common Extravasation

Respiratory, thoracic and mediastinal disorders (4)

Common Cough · dyspnea · epistaxis · respiratory distress

Other (2)

Very Common Dermatologic: Acne vulgaris · pseudofolliculitis barbae

Dosing

Source: Lexicomp

Facial hair reduction (females): Topical: Apply thin layer to affected areas of face and areas under the chin twice daily, at least 8 hours apart Treatment of infections caused by Trypanosoma brucei gambiense infection (sleeping sickness) (off-label use): IV infusion: 100 mg/kg/dose given every 6 hours for 14 days (Kappagoda 2011)

(For additional information see "Eflornithine (United States: Availability of intravenous preparation limited to CDC and WHO distribution programs): Pediatric drug information") Facial hair reduction (females): Children ≥12 years and Adolescents: Refer to adult dosing.

Refer to adult dosing.

There are no dosage adjustments provided in the manufacturer's labeling. Injection: Dose should be adjusted although no specific guidelines are available.

Warnings & Precautions

Source: Lexicomp

Cream

Appropriate use: For topical use by females only; discontinue if hypersensitivity occurs.

Injection

For IV use only; not for IM administration. Must be diluted before use; frequent monitoring for myelosuppression should be done; use with caution in patients with a history of seizures and in patients with renal impairment; serial audiograms should be obtained; due to the potential for relapse, patients should be followed up for at least 24 months.

Pregnancy & Lactation

Pregnancy

FDA category C Teratogenic

When administered topically, teratogenic effects were not observed in animal reproduction studies. Discontinuation or not initiating therapy should be considered since information related to topical use in pregnancy is limited.

Lactation

It is not known if eflornithine is excreted in breast milk. The manufacturer recommends that caution be exercised when administering eflornithine to nursing women.

Monitoring

Clinical pearl	CBC with platelet counts

Chemistry & Properties

Formula	C6H12F2N2O2
Molecular weight	182.17 g/mol
IUPAC name	2,5-diamino-2-(difluoromethyl)pentanoic acid
CAS	70052-12-9
PubChem CID	3009
InChIKey	`VLCYCQAOQCDTCN-UHFFFAOYSA-N`
logP	-0.23 (XLogP -2.9)
Polar surface area	89.34 Å²
H-bond acceptors / donors	3 / 3
Drug-likeness (QED)	0.55
Lipinski violations	0

SMILES

NCCCC(N)(C(=O)O)C(F)F

Biology & Pharmacokinetics

Pharmacokinetics predicted

Bioavailability	10.0%
Half-life	1.916 h
Volume of distribution	0.693 L/kg
Protein binding	7.7%
BBB penetrant	No

Transporters

BCRP (Inhibitor)BSEP (Inhibitor)BSEP (Inhibitor)MRP1 (Inhibitor)MRP3 (Inhibitor)MRP4 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)OCT1 (Inhibitor)P-gp (Inhibitor)P-gp (Substrate)

Registered Products (1)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
Florexa Cream	Cream 13.9 %	30 g tube	PELLA PHARMACEUTICALS CO.LTD/JORDAN	24.500