Naftifine

D01A - Antifungals for topical use ATC D01AE22 Small molecule approved 1988 Topical Natural product

JFDA label: Exoderil Sol

Mechanism of Action

Synthetic, broad-spectrum antifungal agent in the allylamine class; appears to have both fungistatic and fungicidal activity. Exhibits antifungal activity by selectively inhibiting the enzyme squalene epoxidase in a dose-dependent manner which results in a reduced synthesis of ergosterol, the primary sterol within the fungal membrane, and increased squalene in cells.

Indications

Approved

Tinea infections
Tinea pedis

Antimicrobial Spectrum

Expected / intrinsic spectrum (EUCAST breakpoints & labels) — not local resistance. Source: openfda-label.

Fungi

Organism	Activity	MIC
Trichophyton rubrum	Active	—

Contraindications

Source: Lexicomp

Hypersensitivity to naftifine 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

Skin and subcutaneous tissue disorders (5)

Common Burning sensation of skin · erythema · pruritus · skin irritation · xeroderma

General disorders and administration site conditions (1)

Common Application site reaction

Dosing

Source: Lexicomp

Tinea corporis, tinea cruris: Topical: Cream 1% and gel 1%: Apply once daily (cream) or twice daily (gel; morning and evening) to affected area and surrounding skin for up to 4 weeks Cream 2%: Apply a thin layer once daily to affected area and healthy surrounding skin (1/2 inch margin) for 2 weeks Tinea pedis: Topical: Cream 1% and gel 1%: Apply once daily (cream) or twice daily (gel; morning and evening) to affected area and surrounding skin for up to 4 weeks Cream 2% and gel 2%: Apply a thin layer once daily to affected area and surrounding skin (1/2 inch margin) for 2 weeks

Tinea corporis: Children ≥2 years and Adolescents: Topical Cream 2%: Refer to adult dosing. Tinea cruris, tinea pedis: Children ≥12 years and Adolescents: Topical: Cream 2%: Refer to adult dosing. Tinea pedis: Children ≥12 years and Adolescents: Topical: Gel 2%: Refer to adult dosing.

Refer to adult dosing.

There are no dosage adjustments provided in the manufacturer's labeling.

Warnings & Precautions

Source: Lexicomp

Irritation

Discontinue if sensitivity or irritation occurs and institute appropriate therapy. Other warnings/precautions:

Appropriate use

For topical use only; not intended for oral, ophthalmic, or vaginal use. Avoid use of occlusive dressings and contact with eyes, nose, mouth, or mucous membranes.

Pregnancy & Lactation

Pregnancy

FDA category B

Adverse events were not observed in animal reproduction studies following oral administration. Naftifine is absorbed systemically (4% to 6%) following topical administration.

Lactation

It is not known if naftifine is excreted in breast milk. According to the manufacturer, the decision to continue or discontinue breast-feeding during therapy should take into account the risk of infant exposure, the benefits of breast-feeding to the infant, and benefits of treatment to the mother.

Monitoring

Clinical pearl	Culture and KOH exam; re-evaluate if no improvement after 4 weeks of therapy

Chemistry & Properties

Formula	C21H21N
Molecular weight	287.41 g/mol
IUPAC name	(E)-N-methyl-N-(naphthalen-1-ylmethyl)-3-phenylprop-2-en-1-amine
CAS	65472-88-0
PubChem CID	47641
InChIKey	`OZGNYLLQHRPOBR-DHZHZOJOSA-N`
logP	4.99 (XLogP 5.1)
Polar surface area	3.24 Å²
H-bond acceptors / donors	1 / 0
Drug-likeness (QED)	0.64
Lipinski violations	0

SMILES

CN(C/C=C/c1ccccc1)Cc1cccc2ccccc12

Biology & Pharmacokinetics

Pharmacokinetics

BBB penetrant	No

Enzyme interactions

Enzyme	Role	Detail
CYP1A2	Inhibitor	—
CYP1A2	Substrate	—
CYP2B6	Inhibitor	—
CYP2B6	Substrate	—
CYP2C19	Inhibitor	—
CYP2C19	Substrate	—
CYP2C8	Inhibitor	—
CYP2C9	Substrate	—
CYP2D6	Inhibitor	—
CYP2D6	Substrate	—

Transporters

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

Registered Products (1)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
Exoderil Sol	Solution 10 mg/ml	10 ml	Nabulsi Drug Store	2.200