An unacceptable benefit-risk ratio identified for a topical medicine- ‘Bufexamac’ which had been in the Over the Counter (OTC) medicine market since decades.

In Brief

Risks (serous skin ADRs-allergic contact dermatitis leading to hospitalization) Outweighs anticipated benefits (No proven efficacy data, reports of lack of efficacy & Insufficient studies on efficacy)

Bufexamac is a cyclo-oxygenase (COX) inhibitor which is indicated for the relief of dermatitis, rash, and hive. It comes under the drug class- ‘non-steroidal anti-inflammatory drug’ (NSAID). These class of medications produce therapeutic effect by reducing the production of prostaglandins which are involved in inflammation, fever, and pain. It is used in combination with chlorhexidine and lidocaine (lignocaine) in first aid creams that are applied to the skin. These creams are used to treat minor cuts and abrasions; insect bites, stings, and itches; and minor burns and sunburn.

Inadequate evidence on Efficacy:

MedSafe (New Zealand health authority) performed risk-benefit analysis for bufexamac due to insufficient data demonstrating the effectiveness in the intended therapeutic indications and increasing concern of serious adverse skin reactions requiring hospitalizations. MedSafe reviewed medical literature pertaining to efficacy studies which were shared by sponsor. These studies were double blinded and conducted during the period of 1970s and early 1980s, which were not as per the expected standards with current GCP guidelines.

No significant benefit in comparison with alternatives & placebo:

A larger double-blind, controlled, multicentre trial comprising 193 subjects showed that bufexamac has no statistically significant benefit when compared with alternative treatments like triamcinolone and hydrocortisone. Also, there was no statistically significant difference in effectiveness shown by bufexamac and placebo. In brief, no clinical study has provided a good evidence in showing efficacy for bufexamac in the relief of dermatitis. No clinical studies were conducted for bufexamac in the context of other therapeutic indications-rash and hives.

Limited Safety data-due to under-reporting:

Bufexamac is in OTC market segment since many years and the magnitude of underreporting is high for OTC medicines. MedSafe reviewed the available limited safety data from the below sources.

  1. EU-SmPC: In this reference safety information, it was mentioned that bufexamac is indicated for the symptomatic treatment of pruritus from inflammatory skin conditions and the adverse drug reactions section specified the possibility of allergic contact eczema and allergic skin manifestations, which are sometimes extensive or generalised.
  2. Spontaneous data: Review of adverse drug reactions from spontaneous sources revealed contact dermatitis and eczema as most commonly reported adverse events which raised the possibility of lack of drug efficacy. Some of these dermal and epidermal adverse events were serious which resulted in hospitalization. Some other serious adverse events which raised concern due to hospitalizations were condition aggravated, pyrexia and hypersensitivity reactions.
  3. Periodic Safety Update Reports: Review of PSURs for bufexamac topical applications available in Europe identified no new safety signals and no new aspects of existing safety findings.
  4. Medical Literature: MedSafe performed review of available published literature relevant to the safety of bufexamac. This review identified skin-related adverse events, particularly allergic contact dermatitis in most the relevant literature abstracts and articles.
  5. Safety Database: A review of pharmacovigilance database from European sponsor revealed that most of the adverse event reports received were related to skin reactions, many of which suggest allergy. Most the skin ADRs (allergic dermatitis) databased are serious which resulted in hospitalization.

MedSafe concluded that bufexamac containing medicines are associated with a concerning rate of contact allergic reactions and no proven efficacy data in the relief of dermatitis, rash, and hives. The above factors suggested that the balance of benefits and risks is unfavourable for bufexamac containing medicines.

Revocation of marketing authorisations in Europe for bufexamac

On 22-Apr-2010, European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended to revoke marketing authorizations for bufexamac containing medicines from Europe. This recommendation was based on scientific review of efficacy and safety data for bufexamac which involved the concerning serious adverse events of contact allergic reactions associated with bufexamac and availability of very limited data for supporting efficacy of bufexamac.

Benefit-Risk ratio for bufexamac- “No longer considered Positive”

On 08-Sep-2020, Australia health authority- Therapeutic Goods Administration (TGA) released a safety advisory for bufexamac containing medicines concerning the risk of serious skin adverse drug reactions- allergic contact dermatitis. TGA informed health care professionals and consumers that first aid creams containing bufexamac would be removed from the market owing to ‘unacceptable benefit-risk profile’. This decision was taken based on TGA’s scientific review of available safety and limited efficacy data for bufexamac and from independent advice from the Advisory Committee on Medicines (ACM). TGA cancelled the registration of all the bufexamac containing medicinal products effective 18-Sep-2020 and ceased advertisement of first aid creams containing bufexamac.

Voluntary ADR Reporting:

Health care professionals and consumers are advised to report any adverse reactions experienced with the use of medicinal products to the TGA by online voluntary adverse event reporting facility available at TGA online adverse event reporting. This would facilitate in accumulation of the more evident safety data which could expedite the regulatory actions by TGA.

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