Lidocaine Patch 5%
Lidoderm; also ZTlido 1.8% (bioequivalent topical system)
Lidocaine Patch Indications
| Indication | Approved Population | Therapy Type | Status |
|---|---|---|---|
| Post-herpetic neuralgia (PHN) | Adults | Topical monotherapy or adjunct to systemic analgesics | FDA Approved |
The lidocaine patch 5% is a targeted peripheral analgesic that provides analgesia by reducing aberrant firing of sodium channels on damaged pain fibres directly beneath the patch. It was the first topical formulation approved specifically for neuropathic pain. In randomized controlled trials, treatment produced a modest but significant reduction in pain intensity (approximately 10–20 mm on a 100 mm visual analogue scale) and was well tolerated, with adverse events limited primarily to mild application-site reactions. Current clinical guidelines from the AAN and IASP list the lidocaine patch among first-line options for post-herpetic neuralgia, alongside gabapentinoids, tricyclic antidepressants, and SNRIs.
Acute post-operative surgical wound pain — Applied to intact skin adjacent to the incision site. Multiple studies show modest efficacy; data are inconclusive regarding opioid-sparing benefit. Evidence quality: Moderate.
Osteoarthritis pain — Open-label pilot studies demonstrated significant pain reduction and improved function after 2 weeks. Not supported by placebo-controlled RCTs. Evidence quality: Low.
Diabetic peripheral neuropathy — The AAN 2022 guideline update found insufficient evidence to recommend topical lidocaine. An open-label study showed benefit, but a randomized double-blind brain-imaging study found no superiority over placebo. Evidence quality: Low.
Chronic low back pain — A randomized double-blind placebo-controlled study demonstrated no difference from placebo patch. Strong evidence against efficacy. Evidence quality: Low (negative).
Lidocaine Patch Dosing
Dosing — By Clinical Scenario
| Clinical Scenario | Starting Dose | Maintenance Dose | Maximum Dose | Notes |
|---|---|---|---|---|
| Post-herpetic neuralgia — standard adult (Lidoderm 5%) | Up to 3 patches applied once daily | Up to 3 patches for up to 12 h per 24-h period | 3 patches simultaneously; 12 h on, 12 h off | Apply to intact skin covering the most painful area May be cut to smaller sizes with scissors before removing the release liner |
| Post-herpetic neuralgia — ZTlido 1.8% | Up to 3 topical systems once daily | Up to 3 systems for up to 12 h per 24-h period | 3 systems; 12 h on, 12 h off | One ZTlido 1.8% provides equivalent lidocaine exposure to one Lidoderm 5% Different delivery technology; improved adhesion; contains 36 mg lidocaine per system |
| Debilitated patient or impaired elimination | 1–2 patches | Smallest effective area | Reduce number and/or size of patches | Smaller treatment areas recommended; includes patients with severe hepatic disease Monitor for signs of lidocaine toxicity; consider serum lidocaine level if symptomatic |
| OTC lidocaine patch (4%) — minor musculoskeletal pain | 1 patch to affected area | Up to 3 times daily | No more than 8 h per application | Not FDA-approved for neuropathic pain; no comparative trial data vs Rx 5% patch Available as Aspercreme, Salonpas, and other OTC brands |
The FDA-approved dosing schedule requires a mandatory 12-hour patch-free interval each day. This is designed to prevent accumulation of systemically absorbed lidocaine. However, pharmacokinetic studies have shown that even with extended application (18–24 hours) and up to 4 patches, systemic lidocaine concentrations remain well below the toxic threshold of 5 mcg/mL. The mean peak concentration with standard dosing (3 patches, 12 hours) is only ~0.13 mcg/mL. Despite this reassuring safety data, prescribers should adhere to the labelled dosing schedule, particularly in patients with hepatic impairment or those receiving other lidocaine-containing products.
Pharmacology
Mechanism of Action
Lidocaine is an amide-type local anesthetic that stabilises neuronal membranes by inhibiting the ionic fluxes required for the initiation and conduction of nerve impulses. When applied topically via the patch, lidocaine penetrates into the dermis and reduces aberrant ectopic discharges from damaged peripheral nerve fibres that are characteristic of post-herpetic neuralgia. The analgesic effect is peripheral and localised — sensory blockade is limited to the application site, and pain from nociceptive stimuli (pinprick, thermal) in areas distant from the patch is unaffected. Importantly, the patch provides analgesia without producing full local anaesthesia; the vast majority of patients retain sensation to light touch and pinprick under the patch.
ADME Profile
| Parameter | Value | Clinical Implication |
|---|---|---|
| Absorption | Only 3 ± 2% of applied dose absorbed systemically; Cmax ~0.13 mcg/mL with 3 patches × 12 h; absorption proportional to application area and duration; no accumulation with daily use (FDA PI) | Systemic levels are ~1/10 of those needed for cardiac antiarrhythmic effect and well below the toxic threshold of 5 mcg/mL; risk of systemic toxicity is minimal with standard dosing |
| Distribution | Vd 0.7–2.7 L/kg (mean 1.5 ± 0.6, n=15, IV data); ~70% protein-bound to alpha-1-acid glycoprotein; crosses placental and blood-brain barriers (FDA PI) | Protein binding is concentration-dependent at higher levels (1–4 mcg/mL), where binding sites become saturated and the free fraction increases; not clinically relevant at topical patch concentrations (~0.13 mcg/mL); alpha-1-acid glycoprotein rises in inflammation, potentially increasing total binding capacity |
| Metabolism | Hepatic to MEGX (active, 11–36% of lidocaine levels IV) and GX (active, 5–11%); conjugated; minor metabolite 2,6-xylidine (carcinogenic in rats, negligible levels with patch); unknown if skin metabolism occurs (FDA PI) | Patients with severe hepatic disease metabolise lidocaine more slowly and are at greater risk of toxic accumulation; MEGX and GX contribute to both therapeutic and toxic effects |
| Elimination | t1/2 81–149 min (mean 107 ± 22, n=15, IV data); clearance 0.33–0.90 L/min (mean 0.64 ± 0.18); <10% excreted unchanged in urine (FDA PI) | Rapid systemic clearance limits accumulation risk; dialysis is of negligible value in overdose due to large Vd |
Side Effects
| Adverse Effect | Incidence | Clinical Note |
|---|---|---|
| Application site erythema / irritation | Common (similar incidence with lidocaine and vehicle patch in RCTs) | Most frequently reported reaction; generally mild and transient, resolving within minutes to hours; importantly, controlled trials showed this occurs at a comparable rate with placebo (vehicle) patches, indicating it is largely adhesive-related rather than drug-related |
| Application site burning / stinging sensation | Common (frequency not precisely quantified in PI) | Listed in PI among reactions that may develop during or immediately after treatment; remove patch if intolerable and do not reapply until irritation subsides |
| Adverse Effect | Incidence | Clinical Note |
|---|---|---|
| Application site edema / papules / vesicles | 1–7% | Part of the spectrum of local skin reactions described in the PI; includes blisters, depigmentation, discoloration, petechia, and exfoliation |
| Application site pruritus | ~1–5% | May be difficult to distinguish from the underlying PHN itch; typically self-limited |
| Headache | ~3% (OA pilot study, n=134) | Reported in post-marketing surveillance and open-label trials; causality not fully established (FDA PI) |
| Dermatitis (contact) | ~2–3% (OA pilot study) | May represent true allergic contact dermatitis or irritant reaction; discontinue and evaluate if persistent |
| Adverse Effect | Estimated Frequency | Typical Onset | Required Action |
|---|---|---|---|
| Anaphylaxis / angioedema | Very rare | Minutes to hours after application | Immediate removal of all patches; epinephrine, airway management; never re-challenge |
| Methemoglobinaemia | Very rare (case reports with local anaesthetics) | Minutes to hours; may be delayed | Remove patches; check MetHb level; methylene blue 1–2 mg/kg IV if symptomatic; higher risk with G6PD deficiency, infants <6 months, or concurrent oxidizing agents |
| Systemic lidocaine toxicity (CNS and cardiovascular) | Very rare with appropriate use | Excessive dosing, application to non-intact skin, or hepatic impairment; expected above 5 mcg/mL | Remove patches immediately; check lidocaine blood concentration; supportive care; seizure management with benzodiazepines; ACLS for cardiovascular collapse; lipid emulsion for severe toxicity |
| Accidental ingestion by child or pet | Rare (post-marketing reports) | Used patch still contains ≥665 mg lidocaine | Emergency care; poison control; hospital monitoring for CNS and cardiac toxicity |
Even after 12 hours of use, a used lidocaine patch retains at least 665 mg of lidocaine. This is a potentially lethal dose if ingested by a young child or pet. Fold the used patch so the adhesive side sticks to itself and discard safely out of reach of children and animals. This risk is explicitly highlighted in the FDA-approved label and should be part of every patient counselling conversation.
Drug Interactions
The lidocaine patch produces minimal systemic absorption (~0.13 mcg/mL peak), making clinically significant pharmacokinetic interactions extremely unlikely at recommended doses. No drug-drug interactions have been noted in clinical trials. However, the PI warns about additive toxicity with other lidocaine-containing products and Class I antiarrhythmic drugs, and the total dose of all lidocaine formulations must be tracked.
Monitoring
-
Application Site
Each application
Routine Inspect the skin before each application. Do not apply to broken, inflamed, or infected skin. Monitor for erythema, blisters, edema, or allergic contact dermatitis. If burning sensation occurs during application, remove patch and do not reapply until irritation resolves. -
Pain Response
At 2–4 weeks
Routine Assess pain relief using a numerical rating scale or VAS. In the pivotal PHN trial, significant benefit versus vehicle was observed from 4–12 hours after application. If no meaningful pain relief after 2–4 weeks, reassess the diagnosis and consider alternative or adjunctive therapy. -
Lidocaine Blood Level
If toxicity suspected
Trigger-based Check serum lidocaine concentration if signs of systemic toxicity develop (CNS symptoms such as dizziness, tinnitus, visual changes, tremor, or cardiovascular symptoms). Toxicity expected above 5 mcg/mL. Normal peak with 3 patches is only ~0.13 mcg/mL. -
Methemoglobin
If cyanosis develops
Trigger-based Monitor for cyanotic skin discoloration or abnormal blood colouration, especially in patients with G6PD deficiency, infants under 6 months, or those receiving oxidizing agents concurrently. Check co-oximetry if methemoglobinaemia suspected. -
Hepatic Function
Before initiation if hepatic risk factors
Trigger-based Patients with severe hepatic disease are at greater risk of developing toxic blood concentrations due to impaired lidocaine metabolism. Consider using fewer patches and smaller treatment areas. No routine LFT monitoring required for standard patients.
Contraindications & Cautions
Absolute Contraindications
- Known hypersensitivity to local anaesthetics of the amide type (lidocaine, bupivacaine, mepivacaine, prilocaine, ropivacaine) or to any component of the product
Relative Contraindications (Specialist Input Recommended)
- Severe hepatic disease — lidocaine is extensively metabolised hepatically; impaired clearance increases risk of systemic toxicity; use smaller treatment areas and fewer patches
- Application to non-intact skin — broken or inflamed skin may result in substantially higher systemic absorption, although this has not been formally studied
- G6PD deficiency or concurrent oxidizing agents — increased susceptibility to methemoglobinaemia from lidocaine exposure
Use with Caution
- Patients allergic to PABA derivatives (procaine, tetracaine, benzocaine) — although cross-sensitivity has not been shown with amide-type anaesthetics, the PI advises caution when the causative agent is uncertain
- Concurrent use of other lidocaine products — total dose from all formulations must be considered to avoid exceeding safe systemic levels
- Concurrent Class I antiarrhythmic drugs — additive cardiac sodium channel blockade
- Debilitated patients — smaller treatment areas recommended
Cases of methemoglobinaemia have been reported in association with local anaesthetic use, including lidocaine. Signs include cyanotic skin discolouration and abnormal blood colouration that may appear immediately or be delayed. Patients with G6PD deficiency, congenital or idiopathic methemoglobinaemia, cardiac or pulmonary compromise, infants under 6 months of age, and those concurrently exposed to oxidizing agents are at higher risk. If methemoglobinaemia is suspected, discontinue the lidocaine patch and treat with methylene blue (1–2 mg/kg IV) as indicated. MetHb levels may continue to rise, potentially leading to seizures, coma, arrhythmias, and death.
Patient Counselling
Purpose of Therapy
The lidocaine patch is a medicated adhesive plaster applied directly to the skin over the area of pain caused by shingles (post-herpetic neuralgia). It works by blocking pain signals from damaged nerves beneath the patch. It does not numb the skin completely and does not treat the cause of the pain, but it can reduce the intensity of burning, stabbing, and shooting sensations.
How to Apply
Apply the patch to clean, dry, intact skin that is not broken, cut, or irritated. You may use up to 3 patches at once. Wear the patches for a maximum of 12 hours, then remove them and go patch-free for at least 12 hours before applying new patches. The patch may be cut to a smaller size if needed. Clothing may be worn over the patch. Wash your hands after handling the patch and avoid getting it near your eyes.
Sources
- Lidoderm (lidocaine patch 5%). Full Prescribing Information. Endo Pharmaceuticals. NDA 020612. Revised 2018. FDA Label Primary source for dosing (max 3 patches, 12 h on/12 h off), PK data (3% absorption, Cmax 0.13 mcg/mL, t1/2 107 min), adverse reactions, and contraindications.
- ZTlido (lidocaine topical system) 1.8%. Full Prescribing Information. Scilex Pharmaceuticals. NDA 207962. Revised 2018. FDA Label Source for bioequivalent 1.8% topical system (36 mg lidocaine per system) including heat and exercise PK data and adhesion data.
- Galer BS, Rowbotham MC, Perander J, Friedman E. Topical lidocaine patch relieves postherpetic neuralgia more effectively than a vehicle topical patch: results of an enriched enrollment study. Pain. 1999;80(3):533-538. doi:10.1016/S0304-3959(98)00244-9 Pivotal withdrawal-design RCT (n=32): time to exit 14 vs 3.8 days (p<0.001) favouring lidocaine patch; established efficacy for FDA approval.
- Galer BS, Jensen MP, Ma T, Davies PS, Rowbotham MC. The lidocaine patch 5% effectively treats all neuropathic pain qualities: results of a randomized, double-blind, vehicle-controlled, three-week efficacy study with use of the neuropathic pain scale. Clin J Pain. 2002;18(5):297-301. doi:10.1097/00002508-200209000-00004 RCT demonstrating significant improvement across all neuropathic pain qualities measured by the Neuropathic Pain Scale in PHN patients.
- Galer BS, Sheldon E, Patel N, et al. Topical lidocaine patch 5% may target a novel underlying pain mechanism in osteoarthritis. Curr Med Res Opin. 2004;20(9):1455-1458. doi:10.1185/030079904X2754 Open-label pilot study (n=134) demonstrating pain reduction and functional improvement in OA; source for side effect incidence data (10% treatment-related AEs).
- Hashmi JA, Baliki MN, Huang L, et al. Lidocaine patch (5%) is no more potent than placebo in treating chronic back pain when tested in a randomised double blind placebo controlled brain imaging study. Mol Pain. 2012;8:29. doi:10.1186/1744-8069-8-29 Negative RCT demonstrating no superiority over placebo for chronic back pain; important evidence against this off-label use.
- Dworkin RH, O’Connor AB, Backonja M, et al. Pharmacologic management of neuropathic pain: evidence-based recommendations. Pain. 2007;132(3):237-251. doi:10.1016/j.pain.2007.08.033 IASP NeuPSIG guidelines listing topical lidocaine as first-line for localised neuropathic pain, including PHN.
- Price R, Smith D, Franklin G, et al. Oral and topical treatment of painful diabetic polyneuropathy: practice guideline update summary. Neurology. 2022;98(1):31-43. doi:10.1212/WNL.0000000000013038 AAN 2022 guideline update finding insufficient evidence to recommend topical lidocaine for painful diabetic neuropathy; informs off-label evidence rating.
- Gammaitoni AR, Alvarez NA, Galer BS. Safety and tolerability of the lidocaine patch 5%, a targeted peripheral analgesic: a review of the literature. J Clin Pharmacol. 2003;43(2):111-117. doi:10.1177/0091270002239817 Comprehensive safety review confirming minimal systemic absorption, no drug-drug interactions in clinical trials, and predominantly mild local skin reactions.
- Gammaitoni AR, Davis MW. Pharmacokinetics and tolerability of lidocaine patch 5% with extended dosing. Ann Pharmacother. 2002;36(2):236-240. doi:10.1345/aph.1A124 PK study showing that even with extended application (18–24 h) and up to 4 patches, systemic lidocaine levels remain well below toxic thresholds.
- Davies PS, Galer BS. Review of lidocaine patch 5% studies in the treatment of postherpetic neuralgia. Drugs. 2004;64(9):937-947. doi:10.2165/00003495-200464090-00002 Systematic review of clinical trial data confirming efficacy in PHN and safety even with long-term use and in elderly populations.
- Rosielle DA. The Lidocaine Patch. Palliative Care Network of Wisconsin Fast Facts #148. Revised June 2025. PCNOW Evidence-based clinical summary noting modest efficacy (10–20 mm VAS reduction) in PHN, strong evidence against efficacy in chronic low back pain, and limitations of evidence for other uses.