Summary of Product Characteristics (SmPC) - Condyline 0.5% w/v cutaneous solution
1 NAME OF THE MEDICINAL PRODUCT
Condyline 5 mg/ml Cutaneous Solution
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Condyline contains 5 mg/ml podophyllotoxin in vials of 3.5 ml.
For the full list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Cutaneous Solution.
Each pack of Condyline consists of a 3.5 ml amber glass vial containing 5 mg/ml podophyllotoxin in a clear, colourless alcoholic solution.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
For the topical treatment of condylomata acuminata (warts) affecting the penis or the female external genitalia.
4.2 Posology and method of administration
For topical administration.
Adults
Apply twice daily for three consecutive days directly to the warts. Allow to dry after treatment.
Use the applicator provided, applying not more than 50 applicators-full for each treatment.
This three-day treatment may be repeated, if necessary, at weekly intervals for a total of five weeks of treatment. Only a small area or number of warts should be treated at any one time. Care must be taken to avoid application to healthy tissue.
Special Patient Populations
Elderly
No dose adjustment is needed.
Paediatric population
Not recommended in children under 12 years of age.
4.3 Contraindications
Condyline is contraindicated in patients with the following conditions/diseases:
- hypersensitivity to the active substance or to any of the excipients listed in section 6.1;
- inflamed or bleeding lesions;
- open wounds following surgical procedures;
- in combination with other podophyllin containing preparations;
- pregnant or breast-feeding women (see section 4.6);
- Children under 12 years of age.
4.4 Special warnings and precautions for use
Avoid contact with healthy skin.
Lesions in the female and lesions greater than 4cm2 in the male should be treated under direct medical supervision.
The risk of toxicity is increased during simultaneous treatment with other podophyllin containing preparations since these also contain podophyllotoxin and should therefore be avoided.
The risk of systemic toxicity after topical application is increased by the treatment of large areas with excessive amounts for prolonged periods, by the treatment of friable, bleeding, or recently removed warts, and by inadvertent application to normal skin or mucous membranes.
4.5 Interaction with other medicinal products and other forms of interaction
None known
4.6 Fertility, pregnancy and lactation
Pregnancy
There is a limited amount of data from the use of podophyllotoxin in pregnant women. Animal studies are have shown embryofetal toxicity (resorptions, deaths) toxicity (see section 5.3).
Podophyllotoxin should not be used during pregnancy or in women of childbearing potential not using contraception (see section 4.3).
Breast-feeding
There is insufficient information on the excretion of podophyllotoxin in human milk.A risk to the suckling child cannot be excluded. Podophyllotoxin should not be used during breastfeeding (see section 4.3).
Fertility
There are no human data on the effect of podophyllotoxin on fertility. In animal studies podophyllotoxin had no effect on fertility (see section 5.3).
4.7 Effects on ability to drive and use machines
Condyline has no or negligible influence on the ability to drive and use machines.
4.8 Undesirable effects
The following convention is used for the classification of the frequency of an adverse drug reaction (ADR) and is based on the Council for International Organizations of Medical Sciences (CIOMS) guidelines: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000); not known (cannot be estimated from the available data).
| System Organ Class (SOC) | Frequency | Preferred term |
| Nervous system disorders | Not known1 | Burning sensation |
| Skin and subcutaneous tissue disorders | Not known1 | Application site irritation including pruritus, erythema, skin lesion |
| Reproductive system and breast disorders | Not known1 | Balanoposthitis |
| General disorders and administration site conditions | Not known1 | Pain |
- 1. The adverse drug reactions are based on post-marketing reports. Since these reports are from a population of uncertain size and are subject to confounding factors, it is not possible to reliably estimate their frequency, however in reality systemic reactions are rarely seen.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
4.9 Overdose
Symptoms
The risk of systemic toxicity after topical application is increased by the treatment of large areas with excessive amounts for prolonged periods, by the treatment of friable, bleeding, or recently removed warts, and by inadvertent application to normal skin or mucous membranes. Symptoms including nausea, vomiting, abdominal pain and diarrhoea; thrombocytopenia, leukopenia, hepatotoxicity or renal failure may occur. CNS-related adverse events are delayed in onset and prolonged in duration and include acute psychotic reactions, hallucinations, confusion, dizziness, stupor, ataxia, hypotonia, seizures and coma. Peripheral and autonomic neuropathies develop later and may result in paraesthesias, reduced reflexes, muscle weakness, tachycardia, apnoea, orthostatic hypotension, paralytic ileus and urinary retention.
Management
In topical overdosage, wash well with soap and water; if the eyes are involved bathe thoroughly with water or if available, with an appropriate eye-cleaning solution. If accidentally ingested, give stomach washout and monitor electrolyte balance, blood gases, liver function and blood picture.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Antivirals.
ATC code: D06BB04.
Podophyllotoxin is the therapeutically active component of podophyllin, the resin from the root of Pododphyllum species (Berberidaceae).
Podophyllotoxin is an anti-mitotic agent, with a topical action against warts. It is applied locally to the lesion (e.g. wart) and causes destruction of the tissue locally. Podophyllotoxin and its derivatives have a special affinity for the microtubule protein of the mitotic spindle and thus arrest mitosis in metaphase leading to epithelial cell death. It is also caustic to normal skin if applied to it and can be absorbed into the systemic circulation with resultant toxic effects, in particular nausea, vomiting and thrombocytopenia.
5.2 Pharmacokinetic properties
Absorption
The absorption of podophyllotoxin through the skin or mucous membranes is very limited following local application and the systemic exposure expected to be low with the recommended
method of use and dosage. The extent of absorption depends on the concentration used.
Topical application of 0.1 ml of 5 mg/ml podophyllotoxin on an area of 4 cm2 resulted in maximum plasma concentrations of 5 ng/ml after 1-2 hours. After topical application of 0.1-0.15 ml on extreme large lesions the maximum plasma concentrations was 1-17 ng/ml.
Distribution
Owing to its high lipid solubility, it is distributed through the body including the CNS. There
is no accumulation of the substance in serum.
Metabolism
No data are available on the metabolism of podophyllotoxin.
Excretion and Elimination
No data are available on the excretion of podophyllotoxin. The serum half-life varies between 1 to 4.5 hours.
5.3 Preclinical safety data
Podophyllotoxin toxicity in animals is related to its cytotoxic activity.
The repeat dose toxicity of podophyllotoxin has been assessed in multiple species and with multiple routes of administration. GLP toxicity studies included those in rats and dogs. In a 90-day repeat dose dermal toxicity study in rats topical podophyllotoxin induced necrosis, ulceration and/or hyperplasia around the site of administration, as well as corneal lesions and renal pathology at 2 and 10 mg/kg and death at 10 mg/kg. The NOAEL of 0.25 mg/kg was equivalent to the maximum recommended human exposure.
Carcinogenesis
Long-term topical treatment with podophyllotoxin in mice did not cause skin tumours, but epithelial hyperplasia of the skin was observed.
Dietary carcinogenicity studies in mice and rats for 80 weeks or 104 weeks, respectively, were negative for oncogenic effects induced by podophyllotoxin at doses up to 0.3 mg/kg/day.
Mutagenesis
Although studies to assess the genotoxic potential of podophyllotoxin were conducted, a definitive assessment of the potential for mutagenicity could not be concluded. Other studies suggest that podophyllotoxin has aneugenic activity consistent with its pharmacological action as a microtubule inhibitor.
Reproductive and developmental toxicity
Studies in pregnant mice show podophyllotoxin crosses the placenta. Podophyllotoxin was not teratogenic in rabbits administered up to 0.5% podophyllotoxin topically and rats up to 0.21 mg/kg topically. The dose level in rats is approximately equivalent (0.8X) to the maximum recommended human dose based on body surface area comparisons. The doses administered to rabbits were not known. Oral administration of podophyllotoxin was not teratogenic in rats administered at 0.5 and 5 mg/kg. Intraperitoneal administration of podophyllotoxin was not teratogenic up to the highest dose of 5 mg/kg but embryofetal toxicity (resorptions, deaths) was observed at all doses (approximately 2-19 times the maximum recommended human dose based on body surface area comparisons). In a peri/postnatal study, oral administration of podophyllotoxin up to 2.5 mg/kg had no effect on postnatal development of rat offspring. (approximately 10 times the maximum recommended human dose based on body surface area comparisons). In a multi-generational rat fertility and general reproductive performance study, oral administration of podophyllotoxin up to 2.5 mg/kg/day had no effect on fertility in female or male rats. (approximately 10 times the maximum recommended human dose based on body surface area comparisons).
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Lactic acid,
Sodium lactate 60% solution,
Ethanol 96%.
6.2 Incompatibilities
None stated
6.3 Shelf life
The shelf life of the unopened vial is 2 years from the date of manufacture. Once opened, the product has a shelf life of 6 weeks.
6.4 Special precautions for storage
Do not store above 25°C
6.5 Nature and contents of container
Each pack of Condyline consists of a 3.5ml amber glass vial fitted with a child resistant closure. The pack also includes a suitable quantity of special applicators.
6.6 Special precautions for disposal
Condyline is flammable and should be kept away from naked flames. A patient information leaflet is provided with the product giving details on the use and handling of the product.
7 MARKETING AUTHORISATION HOLDER
Takeda UK Limited
1 Kingdom Street,
London,
W2 6BD,
United Kingdom
8 MARKETING AUTHORISATION NUMBER(S)
PL 16189/0037
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
23 January 2009
10 DATE OF REVISION OF THE TEXT
10/05/2022