What it is
Lidocaine is a numbing medicine that has been a standard local anesthetic for more than 70 years. It stops nerves from sending signals, so an area goes numb for a while. It is injected by doctors and dentists, and it also comes in creams, ointments, gels, sprays and skin patches.
For skin products, strength matters. Over-the-counter pain-relief creams in the US may contain 0.5% to 4% lidocaine. Prescription skin products go higher: a 7% cream that also contains a second numbing drug, and patches of up to 10%. Numbing products sold for tattooing, piercing and laser hair removal have been labelled far stronger; one named by the FDA in 2024 was labelled 29.9%. The more lidocaine that reaches the blood through the skin, the greater the risk of seizures and heart-rhythm problems.
Lidocaine, 2-(diethylamino)-N-(2,6-dimethylphenyl)acetamide (C14H22N2O, 234.34 g/mol, CAS 137-58-6), is an amino-amide local anesthetic. It blocks voltage-gated sodium channels in neuronal membranes, inhibiting the ionic fluxes needed to initiate and conduct impulses. Skin products use the free base (octanol:water partition ratio 43 at pH 7.4); solutions, jellies and injections usually use the hydrochloride salt.
Dermal absorption depends on formulation, area, duration, skin integrity, occlusion and temperature. In the Lidoderm label’s pharmacokinetic study, three 5% patches over 420 cm² of intact skin for 12 hours delivered about 64 mg (3 ± 2% of the dose), with a mean peak blood level of 0.13 mcg/mL; the label expects toxicity above 5 mcg/mL. The Bondlido label notes that bioavailability does not necessarily track labelled strength: its 10% system gave exposure equivalent to a 5% system. Lidocaine is about 70% bound to plasma proteins at these levels, is metabolised in the liver to the active metabolites MEGX and GX, and has a plasma elimination half-life of 81 to 149 minutes after intravenous dosing.
Who made it and when
Lidocaine was invented in Stockholm in the early 1940s by two Swedish chemists, Nils Löfgren and Bengt Lundqvist. Their work grew out of research on gramine, a natural substance found in barley; a lab-made relative of it turned out to have a weak numbing effect. The anesthesiologist Torsten Gordh ran the first clinical tests. The Swedish company Astra took the rights and sold it as Xylocaine, and the FDA approved Xylocaine injection in November 1948. It went on to replace procaine as the standard local anesthetic.
Skin products followed: a 5% ointment was approved in 1951, the lidocaine–prilocaine cream EMLA in 1992, the Lidoderm 5% patch for pain after shingles in 1999, the lidocaine–tetracaine cream Pliaglis in 2006, and further prescription patches in 2018 and 2025.
Holmdahl (1998) traces lidocaine to Hans von Euler’s isolation of gramine from chlorophyll-deficient barley mutants and Erdtman’s synthesis of isogramine, which had weak local-anesthetic activity. Erdtman and Löfgren then made further amino-amides, and Löfgren and Lundqvist arrived at 2-diethylaminoaceto-2,6-xylidide, lidocaine; the synthesis is usually dated to 1943. Torsten Gordh’s clinical studies showed a clear advance over the ester anesthetic procaine, and Astra marketed the drug as Xylocaine. Drugs@FDA records approval of Xylocaine injection (NDA 006488) on 19 November 1948.
Topical approvals in Drugs@FDA include Xylocaine 5% ointment (NDA 008048, 1951), EMLA lidocaine 2.5%/prilocaine 2.5% cream (NDA 019941, 1992; brand since discontinued, not for safety reasons, with generics approved), Lidoderm 5% patch (NDA 020612, 1999), Pliaglis lidocaine 7%/tetracaine 7% cream (NDA 021717, 2006), ZTlido 1.8% topical system (NDA 207962, 2018) and Bondlido 10% topical system (NDA 215029, approved 24 September 2025). Lidoderm, ZTlido and Bondlido are indicated for post-herpetic neuralgia.
What the data say
Lidocaine’s numbing effect is not in doubt. The open questions are about specific uses and about safety at high strength.
For long-lasting nerve pain, a 2014 Cochrane review found 12 small studies with 508 people, half in pain after shingles, and judged all of them at high risk of bias. Individual studies favoured lidocaine, but there was no high-quality evidence. A European trial comparing the 5% patch with the oral drug pregabalin reported similar pain relief and far fewer side effects with the patch.
The Lidoderm label reports that only about 3% of a 5% patch’s lidocaine enters the body. FDA advisories warn that much more gets through over larger areas, with longer contact, on broken skin, with heat, or when the skin is covered. A 2006 case report described toxic blood levels in a woman after a 30% lidocaine gel was used during a skin laser treatment.
Efficacy: Derry et al. (Cochrane 2014) included 12 randomised, double-blind studies (508 participants) of a 5% patch, 5% cream, 5% gel and 8% spray in chronic neuropathic pain. All were at high risk of bias, there was no first- or second-tier evidence and efficacy could not be pooled, although most studies favoured lidocaine on some measure. In NCT00414349 (open-label, sponsored by Grünenthal), an interim analysis of 146 patients found 65.3% responders with the 5% plaster versus 62.0% with pregabalin, and drug-related adverse events in 3.9% versus 39.2%.
Toxicity: the Lidoderm label warns of methemoglobinemia, with higher risk in G6PD deficiency, congenital methemoglobinemia, cardiac or pulmonary compromise, infants under 6 months and with oxidising drugs, and of dose-related CNS excitation or depression progressing to convulsions and respiratory arrest, plus bradycardia, hypotension and cardiovascular collapse. Marra et al. (Arch Dermatol 2006) reported laboratory-confirmed toxic serum lidocaine after prolonged exposure to a compounded 30% gel on the face and neck during fractional photothermolysis, attributing it to high concentration combined with laser disruption of the epidermal barrier. FDA’s 2007 advisory described two deaths after large-area, occluded use of compounded lidocaine–tetracaine creams.
Regulatory picture
Three separate facts. First, approval: lidocaine is FDA approved in many injectable and skin products. Over-the-counter skin pain relievers are limited to 0.5% to 4% under FDA’s monograph; the strongest approved skin products found contain 7% (a cream, with tetracaine) and 10% (a patch). The 29.9% cream named by the FDA in 2024 is far above all of these.
Second, compounding: pharmacies may compound with lidocaine for individual patients, but in 2006 the FDA told five pharmacies to stop mass-producing high-strength numbing creams after two deaths were linked to such products.
Third, enforcement: FDA advisories in 2007 and 2009 warned about numbing creams. Since 2024 the agency has sent warning letters to sellers of tattoo and cosmetic numbing products above 4%, including J-CAIN cream labelled 29.9%, and placed some firms on import alert.
Approval: approved since 1948. Nonprescription external analgesics must conform to OTC Monograph M017, a final administrative order under section 505G of the FD&C Act, which permits lidocaine at 0.5% to 4% and does not permit prilocaine or epinephrine; FDA’s warning letters also state that indications related to tattooing and laser cosmetic procedures are not in M017. Products outside those conditions and without an approved application are unapproved new drugs under section 505(a) and misbranded under section 502(ee). The approved prescription cream Pliaglis is labelled for superficial dermatological procedures such as facial laser resurfacing and laser-assisted tattoo removal.
Compounding: recorded as restricted. Lidocaine is a component of FDA-approved drugs, one of the section 503A conditions for a bulk substance usable by 503A pharmacies, but section 503A bars regularly compounding essentially copies of commercially available drugs, and FDA’s 2006 letters targeted standardized creams made for general distribution rather than individual patients.
Enforcement: advisories dated 2007-02-06 and 2009-01-16; six warning letters and import alerts announced 2024-03-26 (named products included a cream labelled 29.9% lidocaine and combinations with prilocaine, tetracaine or epinephrine); further letters in February and April 2025; and a 2026-04-14 manufacturing warning letter to a US maker of 5% lidocaine tattoo sprays.
