FDA warns on skin anesthetic dangers

Medical Tribune March 2009 P6
David Brill

The US FDA has issued a new public alert on skin-numbing drugs, warning of “potentially serious and life-threatening” consequences if products are misused.

Absorption of topical anesthetics from the skin to the bloodstream can cause seizures, arrhythmias, coma and even death, the organization said in a recent news release.

The warning specifically highlights creams, gels and ointments containing lidocaine, prilocaine, tetracaine and benzocaine – products which are available over the counter or by prescription in the US. These are often used in cosmetic and medical procedures, as well as for general relief of pain and itching.

Two women, aged 22 and 25, are already reported to have died in the US from using skin anesthetics prior to laser hair removal. They wrapped their legs in plastic to increase the pain-relieving effects of the creams but developed seizures and died from the toxic effects, the FDA said in a 2007 statement, which first warned about the use of these products.

Consumers should avoid heavy usage across large areas of skin, select products with the lowest possible amount of anesthetic, and avoid applying to broken or irritated skin, the latest warning advises. They are also advised to refrain from wrapping recently-treated skin in plastic or applying heating pads to the area.

Healthcare professionals, meanwhile, “should determine whether adequate pain relief can be safely achieved with a topical anesthetic, or whether a different treatment would be more appropriate,” the health advisory adds.

Dr. Melvin Ee, a consultant dermatologist at the National Skin Centre, Singapore, stressed that the adverse events highlighted by the FDA are rare but said that the warning serves as a timely reminder of the increasing use of skin numbing products in cosmetic and aesthetic procedures.

“I think the warning is important but the context must be taken into consideration,” he said.

“Topical anesthetics within the hospitals are prescribable medications and it is the onus of the prescribing doctor to adhere to safe prescribing. I personally think that if a doctor adheres to safe prescribing and according to the formulary of the medication, these are useful and safe drugs to use. The public should be made aware of the possible side effects of the medication but it must not be sensationalized.”

Ee advised physicians to consider the suitability of a patient’s age and check for allergies, potential interactions with any other medications, and a history of blood disorders or G6PD deficiency before using the products. They should also look for breaks in the skin and assess the required dosage.

Topical anesthetics reduce painful sensations by interfering with sodium and potassium currents in neuronal membranes, thereby preventing depolarization and inhibiting transmission of the signal. Excessive levels in the bloodstream can lead to systemic toxicity, the effects of which are usually manifested through the central nervous and cardiovascular systems.

Ee added, however, that this is outcome is rare and likely only to happen in the context of an overdose. The more common side effects tend to include transient local reactions at the application site, such as edema, paleness, erythema and a mild burning sensation, he said. In very rare circumstances – less than 0.1 percent of cases – application of topical anesthetics in children can result in allergic reactions leading to shock and methemoglobinemia, he added.

The FDA also expressed concerns over a recent trial which reported that lidocaine gel reduced discomfort and improved patient satisfaction when applied ahead of mammography screening. Despite these positive findings and a lack of adverse events there is potential for harm if the technique becomes used more widely, the FDA said, acknowledging the relatively small size of the 418-women study. [Radiology 2008 Sep;248(3):765-72]

PHOENIX trials bring new hope for treatment of psoriasis

Medical Tribune July 2008 P10
David Brill

Ustekinumab seems to be an effective long-term treatment for patients with moderate-to-severe psoriasis, according to two randomized double-blind trials published last month in The Lancet.

The studies, named PHOENIX 1 and 2, found that more than three quarters of patients experienced a 75 percent improvement in symptoms at 12 weeks, following treatment with 90 mg ustekinumab given by subcutaneous injection at weeks 0 and 4. Furthermore, continued dosing every 12 weeks maintained the response up to a year in the majority of patients.

“These results are very impressive and are better than most of the current systemic treatments available and comparable to infliximab,” said Dr. Colin Theng, a consultant dermatologist at the National Skin Centre in Singapore.

Moreover, he added, the 12-weekly dosing schedule offers an advantage over other drugs which need to be taken more frequently.

Ustekinumab is a human monoclonal antibody which targets interleukins 12 and 23. The apparent success of the drug supports the theory that these proteins play a crucial role in the development of psoriasis, the authors say.

Theng, who is also president of the Psoriasis Association of Singapore, said that the drug was “a
very promising treatment for psoriasis.”

“Based on its efficacy and ease of use, it could certainly potentially be used in routine clinical practice. However, the drawbacks of this medication will include the longterm safety profile as this is a relatively new drug and the long-term side effects are unknown,” he said.

“There is also a risk of increased susceptibility of infections and the cost is likely to be prohibitive for its use as a first line treatment in psoriasis.”

PHOENIX 1 involved 766 patients. After 12 weeks, 67.1 percent of those taking ustekinumab had achieved a psoriasis area and severity index (PASI) score of 75 or higher, compared to only 3.1 percent of those who took placebo.

Those whose response continued up to 40 weeks were then randomized to maintenance therapy or withdrawal. At 1 year, those still taking ustekinumab had a significantly better maintenance of the PASI 75 response, according to the log-rank test (P<.0001).

The second trial, comprising 1,230 patients, found that PASI 75 at week 12 was achieved by 75.7 percent of patients taking 45 mg ustekinumab, 66.7 percent of those taking 90 mg ustekinumab, and 3.7 percent of those taking placebo. Those who had responded only partially to treatment at week 28 were re-randomized, either to continue their dosage every 12 weeks or escalate it to 90 mg every 8 weeks. By week 52, 68.8 percent of those in the dose escalation group had an improved response, compared to 33.3 percent of those whose therapy had remained unchanged.