Podofilox (Topical)
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BAN:
Podophyllotoxin
VA CLASSIFICATION
Primary: DE500
Commonly used brand name(s): Condylox.
Another commonly used name is
podophyllotoxin {03}.
Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).
Category:
Antimitotic agent (topical)—
Indications
Accepted
Condyloma acuminatum (treatment)—Podofilox is indicated for the treatment of condyloma acuminatum of the external genital areas; the gel, but not the solution, may be used for perianal warts. Neither the gel nor the solution should be used to treat warts on mucous membranes, including membranous areas of the urethra, rectum, and vagina. {01}
—Using a 3-day-on and 4-day-off treatment regimen of 0.5% podofilox solution for 2 to 4 weeks, 50% of patients (35 of 75 patients) showed clearing of up to 79% of their warts (412 of 524 warts); 35% of the warts reappeared in 60% of these patients {02}. In two multicenter clinical studies using a 3-day-on and 4-day-off treatment regimen of 0.5% gel for 4 weeks, 25.6% of 106 patients and 38.4% of 176 patients showed complete clearing of their anogenital warts {01}.
Pharmacology/Pharmacokinetics
Physicochemical characteristics:
Source—
Synthesized and purified from the plant families Coniferae (species of Juniperus) and Berberidaceae (species of Podophyllum) {01}.
Molecular weight—
414.41 {03}
Mechanism of action/Effect:
The exact mechanism of action for podofilox is unknown. Podofilox is a potent mitotoxic agent that inhibits cell mitosis; cell division stops, other cellular processes are impaired, necrosis occurs, and the affected tissues gradually erode {01}.
Absorption:
Applying 0.05 mL of 0.5% podofilox solution topically to external genitals does not result in detectable serum concentrations; however, applying 0.1 to 1.5 mL results in systemic absorption. Multiple doses do not accumulate. {02}
Half-life:
Elimination—1 to 4.5 hours {01}.
Time to peak concentration:
Topically, 0.1 to 1.5 mL of 0.05% podofilox solution—1 to 2 hours {02}.
Peak serum concentration:
Topically, 0.1 to 1.5 mL of 0.05% podofilox solution—1 to 17 nanograms per mL {02}.
Precautions to Consider
Carcinogenicity
Animal studies have not shown podofilox to be carcinogenic, including one study of podofilox topically administered to mice in doses of 0.04, 0.2, and 1 mg per kg of body weight (mg/kg) a day for 80 weeks {02}.
Mutagenicity
Podofilox is not mutagenic according to the Ames plate reverse mutation assay (at concentrations up to 5 mg podofilox, with or without metabolic activation) and BALB/3T3 cells (at concentrations up to 0.008 micrograms per mL [mcg/mL] without metabolic activation and 12 mcg/mL with activation). Chromosome damage occurs at higher doses; 25 mg/kg (75 mg per square meter of body surface area) of podofilox caused disruption and breakage of chromosomes in vivo in the mouse micronucleus assay {02}.
Pregnancy/Reproduction
Fertility—
Problems in humans have not been documented {02}.
Podofilox did not impair fertility in two generations of rats given daily topical doses of 0.2 mg/kg of body weight (1.18 mg per square meter of body surface area) (corresponding to the recommended human daily dose) during gametogenesis, mating, gestation, parturition, and lactation {02}.
Pregnancy—
Studies have not been done in humans; however, dose-related systemic absorption has occurred {02}.
Podofilox was embryotoxic in rats that were given daily intraperitoneal doses of 5 mg/kg of body weight (29.5 mg per square meter of body surface area; corresponding to 19 times the maximum human recommended dose [MHRD]). It was not teratogenic in rats that were given daily topical doses of 0.21 mg/kg of body weight (2.95 mg per square meter of body surface area; corresponding to two times the MHRD) for 13 days. {02}
FDA Pregnancy Category C {01} {02}.
Breast-feeding
It is not known if podofilox is distributed into breast milk; however, dose-related systemic absorption has occurred and the potential for serious adverse problems exists. {02}
Pediatrics
Appropriate studies on the relationship of age to the effects of podofilox have not been performed in the pediatric population. Safety and efficacy have not been established {02}.
Geriatrics
No information is available on the relationship of age to the effects of podofilox in geriatric patients.
Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).
Risk-benefit should be considered when the following medical problem exists
Sensitivity to podofilox{02}
Side/Adverse Effects
The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:
Those indicating need for medical attention
Incidence more frequent
Bleeding of skin, local —less than 5% for solution, 22.9% for gel{01}{02}
burning feeling of skin, local{01}{02}
dizziness —less than 5% for solution only, indicating systemic absorption{02}
phimosis (problems with foreskin of penis)—less than 5% for solution only{02}
headache —7% for gel only, indicating systemic absorption{01}
hematuria (bloody urine)—less than 5% for solution only{02}
inflammation of skin, local (redness or swelling of skin{01}{02})
itching of skin, local{01}{02}
malodor (bad odor)—less than 5% for solution only{02}
pain during sexual intercourse —less than 5% for solution only{02}
pain of skin, local{01}{02}
scarring of skin —less than 5% for solution only{02}
skin erosion, local{01}{02} (skin ulcers)
vesicle formation (blistering, crusting, or scabbing of treated skin{01}{02})
vomiting —less than 5% for solution only, indicating systemic absorption{02}
Note: Local burning feeling of skin (64% in males, 78% in females), itching of skin (50% in males, 65% in females), and pain of skin (50% in males, 72% in females) occur more frequently in females than in males. Severe reactions occur within the first 2 weeks of beginning treatment and, for the podofilox solution, are more frequent and severe in females than in males. Inflammation of skin (71% in males, 63% in females) occurs more frequently in males than females, and skin ulcers (67% in males and females) occur equally in both genders. {01} {02}
Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
Desquamation, local (peeling of treated skin{01}{02})
chafing or dryness of skin, local{01}{02}
insomnia (trouble in sleeping)—less than 5% for solution only{01}{02}
soreness or tenderness of skin, local{01}{02}
stinging or tingling of skin, local{01}{02}
Incidence less frequent
Discoloration of skin, local (changes in color of treated skin)—for gel only{01}
skin rash —for gel only{01}
Overdose
For more information on the management of overdose or unintentional ingestion, contact a Poison Control Center (see Poison Control Center Listing ).
Clinical effects of overdose
The following effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:
Signs of systemic absorption of topical administration—in order of appearance
Nausea{01}{02}
vomiting{01}{02}
diarrhea{01}{02}
bone marrow depression{01}{02} (chills; fever; sore throat; unusual bleeding or bruising)
oral ulcers{01}{02}
Note: Bone marrow depression occurred following 5 to 10 intravenous doses of 0.5 to 1 mg/kg a day, but was reversible {02}.
Treatment of overdose
Treatment of systemic toxicity or accidental ingestion is essentially supportive {01} {02}.
To decrease absorption—Wash the skin free of any remaining drug {01} {02}.
Supportive care—Patients in whom intentional overdose is known or suspected should be referred for psychiatric consultation.
Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Podofilox (Topical) .
In providing consultation, consider emphasizing the following selected information (» = major clinical significance):
Before using this medication
» Conditions affecting use, especially:
Sensitivity to podofilox
Proper use of this medication
» Carefully reading patient directions that come with medication before using
» Avoiding contact with eyes and mucous membranes, including mucous membranes of vagina, rectum, and urethra; if contact occurs, immediately flushing eyes with water for 15 minutes or thoroughly washing area of mucous membranes with water
» Importance of not using more medication than the amount prescribed or increasing the frequency to greater than 3 times a week or for more than 4 treatment cycles
» Not applying the medication to any other wart without discussing with the physician; not exceeding a total dose of 10 square centimeters
» Proper administration
• Proper use of applicators; not reusing
• Applying medication to approved wart area only
• Washing medication off normal skin
• Drying treated area before allowing it contact with normal skin
• Washing hands and properly discarding applicator(s) after podofilox application
» Proper dosing
Missed dose: Applying as soon as possible, then returning to regular schedule
» Proper storage
Precautions while using this medication
Understanding that podofilox may not prevent wart recurrence or stop new warts from appearing
Contains alcohol and may be flammable; not using near heat, open flame, or while smoking
Side/adverse effects
Signs of potential side effects, especially bleeding of skin, local; burning feeling of skin, local; dizziness (solution only); phimosis (solution only); headache (gel only); hematuria (solution only); inflammation of skin, local; itching of skin, local; malodor (solution only); pain during sexual intercourse (solution only); pain of skin, local; scarring of skin (solution only); skin erosion; vesicle formation; and vomiting (solution only)
General Dosing Information
On advice of the health care professional, the patient should be able to identify the type of warts podofilox can and cannot be applied to and understand the correct method for applying podofilox. It is particularly important not to apply podofilox to squamous cell carcinomas {01} {02}.
If contact with eyes occurs, patient should wash eyes with a large amount of water and seek professional advice {01} {02}.
Hands should be washed before and after administering podofilox {01} {02}.
Area of treatment with podofilox should be completely dry before allowing treated skin to come in contact with normal skin {01} {02}.
Treatment with podofilox should be discontinued if response of wart to podofilox is unsatisfactory after four treatment cycles. Applying podofilox more frequently than recommended will not increase efficacy but can result in increasing the rate of local adverse effects or cause systemic absorption {01} {02}.
Topical Dosage Forms
PODOFILOX GEL
Usual adult dose
Condyloma acuminatum
Topical, to external genital or perianal warts, two times a day for three consecutive days via applicator tip or finger, then treatment should be discontinued for four consecutive days and cycle repeated until there is no visible wart or for up to four treatment cycles. Treatment should be limited to ten square centimeters or less of wart tissue, and the amount applied should not exceed 0.5 grams of gel per day. {01}
Usual adult prescribing limits
Safety and efficacy beyond four treatment cycles have not been established {01}.
Usual pediatric dose
Condyloma acuminatum
Safety and efficacy have not been established {01}.
Strength(s) usually available
U.S.—
0.5% (Rx) [Condylox (alcohol) (butylated hydroxytoluene) (glycerin) (hydroxypropyl cellulose) (lactic acid) (sodium lactate){01}]
Note: Packaging includes an applicator tip {01}.
Packaging and storage:
Store below 40 ºC (104 ºF), preferably between 15 and 30 ºC (59 and 86 ºF), unless otherwise specified by manufacturer {01}.
Auxiliary labeling:
• For external use only.
• Do not freeze.
Additional information:
Podofilox gel is flammable; keep away from open flame {01}.
PODOFILOX TOPICAL SOLUTION
Usual adult dose
Condyloma acuminatum
Topical, to external genital warts, two times a day (every twelve hours) for three consecutive days via applicator tip, then treatment should be discontinued for four consecutive days and cycle repeated until there is no visible wart or for up to four treatment cycles. Treatment should be limited to ten square centimeters or less of wart tissue, and the amount applied should not exceed 0.5 mL of solution per day. {02}
Usual adult prescribing limits
Safety and efficacy beyond four treatment cycles have not been established {02}.
Usual pediatric dose
Condyloma acuminatum
Safety and efficacy have not been established {02}.
Strength(s) usually available
U.S.—
0.5% (Rx) [Condylox (alcohol—95%) (lactic acid) (sodium lactate){02}]
Packaging and storage:
Store below 40 ºC (104 ºF), preferably between 15 and 30 ºC (59 and 86 ºF), unless otherwise specified by manufacturer {02}.
Auxiliary labeling:
• For external use only.
• Do not freeze.
Additional information:
Podofilox is flammable; keep away from open flame {02}.
Revised: 06/27/1998
References
- Condylox gel package insert (Oclassen Pharmaceuticals—US), Rev 3/97, Rec 5/97.
- Condylox solution package insert (Oclassen Pharmaceuticals—US), Rev 4/95, Rec 12/96.
- Canada JR, editor. USP dictionary of USAN and international drug names 1998. Rockville, MD: The United States Pharmacopeial Convention, Inc; 1997. p. 588.
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