Reasons for adding or updating:

• Change to section 4.1 - Therapeutic indications
• Change to section 4.3 - Contraindications
• Change to section 4.4 - Special warnings and precautions for use
• Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
• Change to section 4.7 - Effects on ability to drive and use machines
• Change to section 4.8 - Undesirable effects - how to report a side effect
• Change to section 4.9 - Overdose
• Change to section 5.1 - Pharmacodynamic properties
• Change to section 5.2 - Pharmacokinetic properties
• Change to section 5.3 - Preclinical safety data
• Change to section 10 - Date of revision of the text

Date of revision of text on the SPC: 07-Aug-2015

Legal Category:GSL

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



·         Section 4.1 (Therapeutic Indications): removal of the “Bifonazole is a broad spectrum antifungal agent “indication

·         Section 4.3 (Contraindications): the contraindication “history of hypersensitivity to imidazole antifungal agents or any of the excipients” has been replaced with “hypersensitivity to the active substance or to any of the excipients listed in section 6.1”.

·         Section 4.4 (Special warnings and precautions for use): addition of hypersensitivity warning “Patients with a history of hypersensitivity reactions to other imidazole antifungal agents (e.g. econazole, clotrimazole, miconazole) must take bifonazole-containing products with caution”.

·         Section 4.5 (Interactions with other medicinal products and other forms of interaction): addition of an interaction warning for warfarin and bifonazole – “Limited data suggests that an interaction between topical bifonazole and warfarin may be possible, leading to increases in INR. If bifonazole is used in a patient on warfarin therapy they should be appropriately monitored. Closer monitoring may be required in cases of occlusion and/or application to a large surface area or to broken and damaged skin”.

·         Section 4.7 (Effects on ability to drive and use machines): wording has been changed from “none known” to “Bifonazole cream has no or negligible influence on the ability to drive or use machines”

·         Section 4.8 (Undesirable effects): addition of mandatory wording regarding suspected ADR reporting (Yellow card scheme).

·         Section 4.9 (Overdose): overdose information updated to “No risk of acute intoxication is seen as it is unlikely to occur following a single dermal application of an overdose (application over a large area under conditions favorable to absorption) or inadvertent oral ingestion. However, in the event of accidental oral ingestion, routine measures such as gastric lavage should be performed only if clinical symptoms of overdose become apparent (e.g. dizziness, nausea or vomiting). Gastric lavage should be carried out only if the airway can be protected adequately.”

·         Section 5 (Pharmacodynamics properties): information has been updated to “Pharmacotherapeutic group: Antifungals for dermatological use – Bifonazole. ATC Code: D01A C10. Bifonazole is an imidazole derivative with a broad antimycotic spectrum, which includes dermatophytes, yeasts, moulds and other fungi such as Malassezia furfur. It is also effective against Corynebacterium minutissimum.Bifonazole exerts its anti-fungal action by inhibiting the biosynthesis of ergosterol on two different levels. Inhibition of ergosterol synthesis leads to structural and functional impairment of the cytoplasmic membrane. The resistance situation for bifonazole is favourable. Primary resistant variants of sensitive fungal species are very rare. Investigations so far did not provide any evidence of a development of secondary resistance in primarily sensitive strains.”

·         Section 5 (Pharmacokinetic properties): addition of absorption information – “Absorption Bifonazole penetrates well into infected skin layers. 6 hours after administration concentrations in the various skin layers reach from 1000 μg/cm3 in the top layer of the epidermis (stratum corneum) to 5 μg/cm3 in the stratum papillare. All concentrations determined are thus within a range of reliable antimycotic activity”.

·         Section 5.3 (Preclinical safety data): additional information on reproduction toxicology studies included “In reproduction toxicology studies in rats and rabbits, oral doses of 30 mg/kg body weight resulted in embryotoxicity including lethality. In the rats, bifonazole at oral doses up to 100 mg/kg body weight was not embryotoxic, but a retarded skeletal development in the fetuses was observed at the dose of 100 mg/kg. This fetal effect on the skeletal development can be considered as a secondary effect resulting from the maternal toxicity (a reduction in body weight)”.

·         Section 10 : legal category removed

Reasons for adding or updating:

• New SPC for new product

Legal Category:GSL

Black Triangle (CHM): NO