Podophyllotoxin

D06B - Chemotherapeutics for dermatological use ATC D06BB04 Small molecule approved 1990 Topical Natural product

JFDA label: Condyline Soln. 0.5%

Mechanism of Action

— Unknown

Indications

Approved

Carcinoma, Squamous Cell — squamous cell carcinoma
Condylomata Acuminata — anogenital venereal wart
Virus Diseases — viral disease

Contraindications

Source: Lexicomp

Hypersensitivity or intolerance to 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

Nervous system disorders (3)

Very Common local pain · Localized burning

Common Headache

Blood and lymphatic system disorders (1)

Very Common Local hemorrhage, local pruritus

Skin and subcutaneous tissue disorders (3)

Very Common Skin erosion

Common erythema · Stinging of the skin

General disorders and administration site conditions (2)

Very Common Local inflammation · local pruritus

Dosing

Source: Lexicomp

Genital warts: Topical: Solution: Apply twice daily (morning and evening) for 3 consecutive days, then withhold use for 4 consecutive days; this cycle may be repeated up to 4 times until there is no visible wart tissue; maximum dose: 0.5 mL daily (or ≤10 cm2 of wart tissue). Note: Discontinue after 4 treatment cycles if incomplete response and consider alternative treatment; do not repeat use. Genital and perianal warts: Topical: Gel: Apply twice daily (morning and evening) for 3 consecutive days, then withhold use for 4 consecutive days; this cycle may be repeated up to 4 times until there is no visible wart tissue; maximum dose: 0.5 g daily (or ≤10 cm2 of wart tissue). Note: Discontinue after 4 treatment cycles if incomplete response and consider alternative treatment; do not repeat use.

Refer to adult dosing.

Warnings & Precautions

Source: Lexicomp

Skin reactions

Most skin reactions are mild to moderate and did not increase during the treatment period, however severe skin reactions can occur. Severe reactions are most frequent within the first two weeks of treatment. Dosage form specific issues:

Topical gel and solution

Flammable; keep away from fire or flame. Other warnings/precautions:

Appropriate use

For cutaneous use only; avoid contact with eyes. If product comes in contact with the eyes, flush with water and seek medical attention. Not intended for treatment of mucous membrane warts.

Pregnancy & Lactation

Pregnancy

FDA category C Teratogenic

Teratogenic events have not been observed in animal reproduction studies with topical administration. Podofilox should not be used during pregnancy (CDC [Workowski 2015])

Lactation

It is not known if podofilox is excreted in breast milk. Due to the potential for adverse reactions in the nursing infant, the manufacturer recommends a decision be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the treatment to the mother.

Monitoring

Clinical pearl	Treated areas for adequate healing; tolerability of treatment

Chemistry & Properties

Formula	C22H22O8
Molecular weight	414.41 g/mol
IUPAC name	(5R,5aR,8aR,9R)-5-hydroxy-9-(3,4,5-trimethoxyphenyl)-5a,6,8a,9-tetrahydro-5H-[2]benzofuro[5,6-f][1,3]benzodioxol-8-one
CAS	518-28-5
PubChem CID	10607
InChIKey	`YJGVMLPVUAXIQN-XVVDYKMHSA-N`
logP	2.41 (XLogP 2.0)
Polar surface area	92.68 Å²
H-bond acceptors / donors	8 / 1
Drug-likeness (QED)	0.76
Lipinski violations	0

SMILES

COc1cc([C@@H]2c3cc4c(cc3[C@H](O)[C@H]3COC(=O)[C@H]23)OCO4)cc(OC)c1OC

Biology & Pharmacokinetics

Pharmacokinetics predicted

Bioavailability	10.0%
Half-life	2.353 h
Volume of distribution	0.507 L/kg
Protein binding	97.4%
BBB penetrant	Yes

Enzyme interactions

Enzyme	Role	Detail
CYP2B6	Inhibitor	—
CYP2C19	Inhibitor	IC₅₀ 4.999999999999999 µM
CYP2C19	Substrate	—
CYP2C8	Inhibitor	—
CYP2C9	Inhibitor	IC₅₀ 4.000000000000001 µM
CYP2D6	Inhibitor	—
CYP3A4	Inhibitor	IC₅₀ 0.5999999999999996 µM
CYP3A4	Substrate	—

Transporters

BCRP (Inhibitor)BSEP (Inhibitor)MRP1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)P-gp (Inhibitor)MDR1 (Substrate)P-gp (Substrate)

Registered Products (1)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
Condyline Soln.	Solution 0.5 %	3.5 ml	Ibn Rushd Drug Store	15.410