Wartec(r) Cream Podophyllotoxin 0.15% w/w
Wartec Cream contains podophyllotoxin 0.15% w/w in a white cream base for topical application.
Wartec Cream is indicated for the topical treatment of external condylomata acuminata (anogenital warts).
Wartec Cream is for topical application only. The affected area should be thoroughly washed with soap and water, and dried prior to application. Using a fingerstall or disposable glove, the cream is applied twice daily morning and evening (every 12 hours) for 3 consecutive days and then withheld for the next 4 consecutive days, using only enough cream to just cover each wart. Hands should be washed thoroughly after application. Application to the surrounding normal tissue should be avoided. Residual warts should be treated with further courses of twice daily applications for three days at weekly intervals, if necessary for a total of 4 weeks of treatment. Where lesions are greater than 4cm2, it is recommended that treatment takes place under the direct supervision of medical staff. There is a possibility of relapse following treatment and in the event that this does occur, alternative treatment may need to be considered.
Renal impairment
No dosage adjustment is necessary. As there is very limited percutaneous absorption of podophyllotoxin with the recommended dosage, renal impairment is not expected to result in systemic exposure of clinical significance.
Hepatic impairment
No dosage adjustment is necessary. As there is very limited percutaneous absorption of podophyllotoxin with the recommended dosage, hepatic impairment is not expected to result in systemic exposure of clinical significance.
Do not use:
on open or bleeding wounds (e.g. following surgical procedures)
in children
if there is hypersensitivity to podophyllotoxin
concomitantly with other podophyllotoxin containing preparations
in pregnancy or lactation
Where the area of treatment is greater than 4 cm2, it is recommended that treatment takes place under the direct supervision of a healthcare professional. Podophyllotoxin should be used with caution in patients with known hypersensitivity to any of the ingredients. Avoid applying podophyllotoxin to warts occurring on mucous membranes of the genital area (including the urethra, rectum and vagina). Contact with eyes should be avoided. If contact occurs, the patient should be advised to rinse the eye with plenty of water, and seek medical advice. Avoid applying podophyllotoxin cream to surrounding healthy tissue. Prolonged contact with healthy skin must be avoided since the cream contains an active pharmaceutical substance, which could be harmful on healthy skin. Occlusive dressings should not be used on areas treated with podophyllotoxin. If severe local skin reactions occur (bleeding, swelling, excessive pain, burning, itching) podophyllotoxin should be washed immediately from the treatment area with mild soap and water, the treatment discontinued and the patient advised to seek medical advice. It is recommended that patients refrain from sexual intercourse while treating warts with podophyllotoxin and until the skin has healed. If a patient does engage in sexual intercourse, a condom must be used.
Use in Pregnancy
The product is not for use in pregnancy (see Contraindications).. There are limited data from the use of podophyllotoxin in pregnant women. Although there is very limited systemic absorption from topically applied podophyllotoxin, antimitotic products such as podophyllotoxin are known to be embryotoxic. Topical podophyllotoxin is not recommended during pregnancy or in women of childbearing potential not using contraception. Podophyllotoxin was embryotoxic (decreased number of foetuses and foetal weight), but not teratogenic in rats when administered intraperitoneally to pregnant females at a dose of 5 mg/kg, approximately 19 times the recommended human dose.
Effects on Fertility
There are no data on the effects of podophyllotoxin on human fertility. Podophyllotoxin was not judged a hazard to male or female fertility in several oral 2- generation rat studies and a female rat dermal general reproductive performance study.
Use in Lactation
The product is not for use in lactation (see Contraindications). There is insufficient information on the excretion of topically applied podophyllotoxin in human milk. A risk to the newborns/infants cannot be excluded.
Paediatric use
Safety and efficacy of topical podophyllotoxin have not been established in children under the age of 12. (See Contraindications).
Use in the elderly
There are no specific recommendations for use in the elderly.
Effects On Ability To Drive And Use Machines
No effects are anticipated based on the adverse reaction profile.
Other
Carcinogenicity
Podophyllotoxin was not mutagenic in an Ames Test, using Salmonella typhimurium strains TA1535, TA1537, TA98 and TA100 up to 5000 ug/plate, the maximum concentration in accordance with current guidelines, and was negative in an in vitro human chromosome aberration assay using human lymphocytes and an in vivo mouse micronucleus test when tested up to 20 mg/kg. Assessment of mutations at the HPRT locus using Chinese Hamster Ovary (CHO) cells in vitro showed evidence of mutagenicity, but the results were inconsistent with regard to the dose response observed across replicate cultures. No oncogenic effects were observed with podophyllotoxin when assessed in two 80- week mouse carcinogenicity studies following dermal or dietary administration, and in a 2-year rat dietary carcinogenicity study. Animal studies published to date have shown podophyllotoxin to be non-carcinogenic.
Clinical trial data
Adverse drug reactions (ADRs) are listed below by MedDRA system organ class and by frequency. Frequencies are defined as: very common (>=1/10), common (>=1/100 and <1/10), uncommon (>=1/1,000 and <1/100), rare (>=1/10,000 and <1/1,000) and very rare (<1/10,000), including isolated reports.
Skin and subcutaneous tissue disorders
Very common Skin erosion, application site irritation (including erythema, pruritus, skin burning sensation)
Post Marketing Data
Immune system disorders
Rare Application site hypersensitivity
Skin and subcutaneous tissue disorders
Rare Skin ulcer, scab, skin discoloration, blister, dry skin
General disorders and administration site conditions
Rare Application site pain, swelling, application site bleeding
Injury, poisoning and procedural complications
Rare Caustic injury, excoriation, wound secretion
None presently known.
In cases of overdosage, contact the Poisons Information Centre on 0800 POISON (0800 764 766). While serious systemic effects have not been reported with the recommended dosage of topical podophyllotoxin, topical overdosage would be expected to increase systemic absorption of the drug and increase the potential for systemic effects, e.g. altered mental state and bone marrow suppression. Excessive use of podophyllotoxin 0.5% solution has been reported as causing two cases of severe local reactions. In cases of excessive use of Wartec Cream resulting in several local reaction, the treatment should be stopped, the area washed and symptomatic treatment introduced. Following oral ingestion, podophyllotoxin may also cause severe gastroenteritis. If topical overdosage occurs, podophyllotoxin should be washed immediately from the treatment area and symptomatic and supportive therapy initiated. Treatment of oral podophyllotoxin poisoning is symptomatic and should include supportive care. Further management should be as clinically indicated or as recommended by the New Zealand National Poisons Centre.
Actions
Podophyllotoxin is a metaphase inhibitor in dividing cells binding to at least one binding site on tubulin. Binding prevents tubulin polymerisation required for microtubule assembly. At higher concentrations, podophyllotoxin also inhibits nucleoside transport through the cell membrane. The chemotherapeutic action of podophyllotoxin is assumed to be due to inhibition of growth and the ability to invade the tissue of the viral infected cells.
Pharmacokinetics
Absorption/Distribution/Metabolism/Excretion
Systemic absorption of podophyllotoxin after topical application of 100 mg of 0.3% cream or 100 uL of 0.5% solution has been studied (extravaginally in 10 females, and within the preputial cavity in 10 males, each on 2 occasions separated by 8 hours). Cmax was at or below 4.7 ng/mL following all doses and Tmax ranged from 0.5 to 36 hrs; in some subjects concentrations were below the limit of detection. Cmax and Tmax were comparable for the 0.3% cream and 0.5% solution in both males and females. It can be concluded that systemic absorption of recommended doses of podophyllotoxin cream or solution is expected to be low.
Other
Chemical Structure
Podophyllotoxin
Excipients
Wartec Cream also contains purified water, stearyl alcohol, cetyl alcohol, isopropyl myristate, liquid paraffin, fractionated coconut oil, butylated hydroxyanisole (BHA), steareth-7, steareth-10, phosphoric acid, methyl hydroxybenzoate, propyl hydroxybenzoate and sorbic acid.
Incompatibilities
None.
Shelf Life
According to stability results, Wartec Cream has a shelf life of three years from the date of manufacture, when stored at the recommended conditions.
Special Precautions for Storage
Wartec Cream should be stored at temperatures not exceeding 30oC.
Wartec Cream contains 0.15% w/w podophyllotoxin in a cream formulation for topical application. The product is presented in lacquered aluminium membrane sealed tubes fitted with a polyethylene cap. A small mirror is supplied with the pack. Pack size: 5 g.
Prescription Medicine.
Distributed by: GlaxoSmithKline NZ Ltd Private Bag 106600 Auckland 1143 NEW ZEALAND
10 April 2012 Version 4.0 Trade Mark: Wartec(r) is a registered trade mark of Stiefel Laboratories, Inc.